@article{%a1.%Y_151,

title = {Collagen VI Deficiency Impairs Tendon Fibroblasts Mechanoresponse in Ullrich Congenital Muscular Dystrophy},

author = {Cenni V and Sabatelli P and Di Martino A and Merlini L and Antoniel M and Squarzoni S and Neri S and Santi S and Metti S and Bonaldo P and Faldini C.},

url = {https://www.mdpi.com/2073-4409/13/5/378},

doi = {10.3390/cells13050378},

year  = {2024},

date = {2024-08-06},

journal = {Cells},

volume = {13},

issue = {5},

pages = {378},

abstract = {The pericellular matrix (PCM) is a specialized extracellular matrix that surrounds cells. Interactions with the PCM enable the cells to sense and respond to mechanical signals, triggering a proper adaptive response. Collagen VI is a component of muscle and tendon PCM. Mutations in collagen VI genes cause a distinctive group of inherited skeletal muscle diseases, and Ullrich congenital muscular dystrophy (UCMD) is the most severe form. In addition to muscle weakness, UCMD patients show structural and functional changes of the tendon PCM. In this study, we investigated whether PCM alterations due to collagen VI mutations affect the response of tendon fibroblasts to mechanical stimulation. By taking advantage of human tendon cultures obtained from unaffected donors and from UCMD patients, we analyzed the morphological and functional properties of cellular mechanosensors. We found that the length of the primary cilia of UCMD cells was longer than that of controls. Unlike controls, in UCMD cells, both cilia prevalence and length were not recovered after mechanical stimulation. Accordingly, under the same experimental conditions, the activation of the Hedgehog signaling pathway, which is related to cilia activity, was impaired in UCMD cells. Finally, UCMD tendon cells exposed to mechanical stimuli showed altered focal adhesions, as well as impaired activation of Akt, ERK1/2, p38MAPK, and mechanoresponsive genes downstream of YAP. By exploring the response to mechanical stimulation, for the first time, our findings uncover novel unreported mechanistic aspects of the physiopathology of UCMD-derived tendon fibroblasts and point at a role for collagen VI in the modulation of mechanotransduction in tendons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_100,

title = {Immunoelectron Microscopy Methods},

author = {Squarzoni S},

url = {https://link.springer.com/protocol/10.1007/978-1-0716-3143-0_15},

doi = {10.1007/978-1-0716-3143-0_15},

year  = {2023},

date = {2023-08-08},

journal = {Methods in molecular biology},

volume = {2655},

pages = {201-210},

abstract = {"Immunoelectron microscopy" defines a group of techniques developed for visualizing where components of cells or tissues are localized, by means of a transmission electron microscope (TEM) at a subcellular resolution. The method is based on antigen recognition by primary antibodies and subsequent visualization of recognized structures by means of electron-opaque gold granules, which are easily visible in TEM images. The potentially high resolution of this method relies on the very small size of the colloidal gold label, which consists of granules ranging from 1 to 60 nm in diameter, mostly used in the 5-15 nm sizes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_45,

title = {3D ECM-rich environment sustains the identity of naive human iPSCs},

author = {Cesare E and Urciuolo A and Stuart HT and Torchio E and Gesualdo A and Laterza C and Gagliano O and Martewicz S and Cui M and Manfredi A and Di Filippo L and Sabatelli P and Squarzoni S and Zorzan I and Betto RM and Martello G and Cacchiarelli D and Luni C and Elvassore N},

url = {https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00458-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590922004581%3Fshowall%3Dtrue},

doi = {10.1016/j.stem.2022.11.011},

year  = {2022},

date = {2022-03-24},

urldate = {2022-03-24},

journal = {Cell stem cell},

volume = {29},

issue = {12},

pages = {1703-1717},

abstract = {The establishment of in vitro naive human pluripotent stem cell cultures opened new perspectives for the study of early events in human development. The role of several transcription factors and signaling pathways have been characterized during maintenance of human naive pluripotency. However, little is known about the role exerted by the extracellular matrix (ECM) and its three-dimensional (3D) organization. Here, using an unbiased and integrated approach combining microfluidic cultures with transcriptional, proteomic, and secretome analyses, we found that naive, but not primed, hiPSC colonies are characterized by a self-organized ECM-rich microenvironment. Based on this, we developed a 3D culture system that supports robust long-term feeder-free self-renewal of naive hiPSCs and also allows direct and timely developmental morphogenesis simply by modulating the signaling environment. Our study opens new perspectives for future applications of naive hiPSCs to study critical stages of human development in 3D starting from a single cell.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__492,

title = {A new Ag-nanostructured hydroxyapatite porous scaffold: Antibacterial effect and cytotoxicity study.},

author = {Calabrese G and Petralia S and Franco D and Nocito G and Fabbi C and Forte L and Guglielmino S and Squarzoni S and Traina F and Conoci S},

url = {https://www.sciencedirect.com/science/article/pii/S0928493120333129?via%3Dihub},

doi = {10.1016/j.msec.2020.111394},

year  = {2021},

date = {2021-03-09},

journal = {Materials science & engineering. C, Materials for biological applications},

volume = {118},

pages = {111394},

abstract = {111394},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__496,

title = {Antimicrobial Effect and Cytotoxic Evaluation of Mg-Doped Hydroxyapatite Functionalized with Au-Nano Rods},

author = {Franco D and Calabrese G and Petralia S and Neri G and Corsaro C and Forte L and Squarzoni S and Guglielmino S and Traina F and Fazio E and Conoci S},

url = {https://www.mdpi.com/1420-3049/26/4/1099},

doi = {10.3390/molecules26041099},

year  = {2021},

date = {2021-03-09},

journal = {Molecules},

volume = {26},

number = {4},

pages = {1099},

abstract = {Hydroxyapatite (HA) is the main inorganic mineral that constitutes bone matrix and represents the most used biomaterial for bone regeneration. Over the years, it has been demonstrated that HA exhibits good biocompatibility, osteoconductivity, and osteoinductivity both in vitro and in vivo, and can be prepared by synthetic and natural sources via easy fabrication strategies. However, its low antibacterial property and its fragile nature restricts its usage for bone graft applications. In this study we functionalized a MgHA scaffold with gold nanorods (AuNRs) and evaluated its antibacterial effect against S. aureus and E. coli in both suspension and adhesion and its cytotoxicity over time (1 to 24 days). Results show that the AuNRs nano-functionalization improves the antibacterial activity with 100% bacterial reduction after 24 h. The toxicity study, however, indicates a 4.38-fold cell number decrease at 24 days. Although further optimization on nano-functionalization process are needed for cytotoxicity, these data indicated that Au-NRs nano-functionalization is a very promising method for improving the antibacterial properties of HA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__504,

title = {Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice.},

author = {Squarzoni S and Schena E and Sabatelli P and Mattioli E and Capanni C and Cenni V and D'Apice MR and Andrenacci D and Sarli G and Pellegrino V and Festa A and Baruffaldi F and

Storci G and Bonafè M and Barboni C and Sanapo M and Zaghini A and Lattanzi G},

url = {https://onlinelibrary.wiley.com/doi/10.1111/acel.13285},

doi = {10.1111/acel.13285},

year  = {2021},

date = {2021-03-09},

urldate = {2021-03-09},

journal = {Aging Cell},

volume = {20},

number = {1},

pages = {e13285},

abstract = {Hutchinson-Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin-6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin-6 activity by tocilizumab, a neutralizing antibody raised against interleukin-6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G / G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging-related disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_431,

title = {A new Ag-nanostructured hydroxyapatite porous scaffold: Antibacterial effect and cytotoxicity study. },

author = {Calabrese G and Petralia S and Franco D and Nocito G and Fabbi C and Forte L and Guglielmino S and Squarzoni S and Traina F and Conoci S},

url = {https://www.sciencedirect.com/science/article/pii/S0928493120333129?via%3Dihub},

doi = {10.1016/j.msec.2020.111394},

year  = {2020},

date = {2020-01-01},

journal = {Materials science & engineering. C, Materials for biological applications},

volume = {118},

pages = {111394},

abstract = {We report a new chemical method for the functionalization of Mg-hydroxyapatite (Mg-HA) scaffold with Ag nanoparticles (Ag NPs) integrating in one step both the synthesis of the Ag NPs and their nano-structuring into the HA matrix (Ag-Mg-HA scaffold). This method exploits a green photochemical synthesis and allows the direct growth of Ag NPs on the Mg-HA surface. The surface structure of Ag-Mg-HA scaffold, investigated by scanning electron microscopy, shows no significant changes in the morphology upon Ag NPs incorporation. The presence of Ag was confirmed by EDX analysis. TEM and spectroscopic investigations show Ag NPs spherical shaped with a mean diameter of about 20 nm exhibiting the typical plasmon absorption band with maximum at 420 nm. The antibacterial properties of Ag-Mg-HA scaffolds were tested against two bacterial strains, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results show excellent antibacterial properties achieving up to 99% and 100% reduction of colonies for both bacteria cultures after 24 h of incubation and 100% of reduction after 48 h of incubation. The cytotoxicity of Ag-Mg-HA was also in deep investigated assessing both cell proliferation and differentiation using hADSCs (human Adipose Derived Stem Cells) and testing data point at 0, 7, 14 and 24 days. The results show cytotoxic effect with cell proliferation decreasing up to 90% at 24 days and osteogenic differentiation inhibition. The observed cytotoxicity can be probable ascribed to the oxidative stress by ROS. Indeed, considering the effectiveness of the nanofunctionalization method and the excellent antibacterial properties showed by the Ag-Mg-HA scaffold, future works will be devoted to create nanofunctionalized scaffold satisfying both antimicrobial and osteo-regenerative properties.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_436,

title = {Emerin Phosphorylation during the Early Phase of the Oxidative Stress Response Influences Emerin-BAF Interaction and BAF Nuclear Localization},

author = {Cenni V and Squarzoni S and Loi M and Mattioli E and Lattanzi G and Capanni C},

url = {https://www.mdpi.com/2073-4409/9/6/1415},

doi = {10.3390/cells9061415},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Cells},

volume = {9},

number = {6},

pages = {1415},

abstract = {Reactive Oxygen Species (ROS) are reactive molecules required for the maintenance of physiological functions. Oxidative stress arises when ROS production exceeds the cellular ability to eliminate such molecules. In this study, we showed that oxidative stress induces post-translational modification of the inner nuclear membrane protein emerin. In particular, emerin is phosphorylated at the early stages of the oxidative stress response, while protein phosphorylation is abolished upon recovery from stress. A finely tuned balance between emerin phosphorylation and O-GlcNAcylation seems to govern this dynamic and modulates emerin-BAF interaction and BAF nucleoplasmic localization during the oxidative stress response. Interestingly, emerin post-translational modifications, similar to those observed during the stress response, are detected in cells bearing LMNA gene mutations and are characterized by a free radical generating environment. On the other hand, under oxidative stress conditions, a delay in DNA damage repair and cell cycle progression is found in cells from Emery-Dreifuss Muscular Dystrophy type 1, which do not express emerin. These results suggest a role of the emerin-BAF protein platform in the DNA damage response aimed at counteracting the detrimental effects of elevated levels of ROS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_435,

title = {Lamin A Involvement in Ageing Processes},

author = {Cenni V and Capanni C and Mattioli E and Schena E and Squarzoni S and Bacalini MG and Garagnani P and Salvioli S and Franceschi C and Lattanzi G},

url = {https://www.sciencedirect.com/science/article/pii/S1568163719302107},

doi = {10.1016/j.arr.2020.101073},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Ageing research reviews},

volume = {62},

pages = {101073},

abstract = {Lamin A, a main constituent of the nuclear lamina, is the major splicing product of the LMNA gene, which also encodes lamin C, lamin A delta 10 and lamin C2. Involvement of lamin A in the ageing process became clear after the discovery that a group of progeroid syndromes, currently referred to as progeroid laminopathies, are caused by mutations in LMNA gene. Progeroid laminopathies include Hutchinson-Gilford Progeria, Mandibuloacral Dysplasia, Atypical Progeria and atypical-Werner syndrome, disabling and life-threatening diseases with accelerated ageing, bone resorption, lipodystrophy, skin abnormalities and cardiovascular disorders. Defects in lamin A post-translational maturation occur in progeroid syndromes and accumulated prelamin A affects ageing-related processes, such as mTOR signaling, epigenetic modifications, stress response, inflammation, microRNA activation and mechanosignaling. In this review, we briefly describe the role of these pathways in physiological ageing and go in deep into lamin A-dependent mechanisms that accelerate the ageing process. Finally, we propose that lamin A acts as a sensor of cell intrinsic and environmental stress through transient prelamin A accumulation, which triggers stress response mechanisms. Exacerbation of lamin A sensor activity due to stably elevated prelamin A levels contributes to the onset of a permanent stress response condition, which triggers accelerated ageing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_100,

title = {Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models.},

author = {Zaghini A and Sarli G and Barboni C and Sanapo M and Pellegrino V and Diana A and Linta N and Rambaldi J and {D'Apice MR} and Murdocca M and Baleani M and Baruffaldi F and Fognani R and Mecca R and Festa A and Papparella S and Paciello O and Prisco F and Capanni C and Loi M and Schena E and Lattanzi G and Squarzoni S},

url = {https://www.sciencedirect.com/science/article/pii/S0531556519304127?via%3Dihub},

doi = { 10.1016/j.exger.2019.110784},

year  = {2020},

date = {2020-03-04},

urldate = {2020-03-04},

journal = {Experimental gerontology},

volume = {130},

pages = {110784},

abstract = {The transgenic LmnaG609G progeric mouse represents an outstanding animal model for studying the human Hutchinson-Gilford Progeria Syndrome (HGPS) caused by a mutation in the LMNA gene, coding for the nuclear envelope protein Lamin A/C, and, as an important, more general scope, for studying the complex process governing physiological aging in humans. Here we give a comprehensive description of the peculiarities related to the breeding of LmnaG609G mice over a prolonged period of time, and of many features observed in a large colony for a 2-years period. We describe the breeding and housing conditions underlining the possible interference of the genetic background on the phenotype expression. This information represents a useful tool when planning and interpreting studies on the LmnaG609G mouse model, complementing any specific data already reported in the literature about this model since its production. It is also particularly relevant for the heterozygous mouse, which mirrors the genotype of the human pathology however requires an extended time to manifest symptoms and to be carefully studied. Copyright 2019 The Authors. Published by Elsevier Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_484,

title = {Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models.},

author = {Zaghini A and Sarli G and Barboni C and Sanapo M and Pellegrino V and Diana A and Linta N and Rambaldi J and D'Apice MR and Murdocca M and Baleani M and Baruffaldi F and Fognani R and Mecca R and Festa A and Papparella S and Paciello O and Prisco F and Capanni C and Loi M and Schena E and Lattanzi G and Squarzoni S},

url = {https://www.sciencedirect.com/science/article/pii/S0531556519304127?via%3Dihub},

doi = {10.1016/j.exger.2019.110784},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Experimental gerontology},

volume = {130},

pages = {110784},

abstract = {The transgenic LmnaG609G progeric mouse represents an outstanding animal model for studying the human Hutchinson-Gilford Progeria Syndrome (HGPS) caused by a mutation in the LMNA gene, coding for the nuclear envelope protein Lamin A/C, and, as an important, more general scope, for studying the complex process governing physiological aging in humans. Here we give a comprehensive description of the peculiarities related to the breeding of LmnaG609G mice over a prolonged period of time, and of many features observed in a large colony for a 2-years period. We describe the breeding and housing conditions underlining the possible interference of the genetic background on the phenotype expression. This information represents a useful tool when planning and interpreting studies on the LmnaG609G mouse model, complementing any specific data already reported in the literature about this model since its production. It is also particularly relevant for the heterozygous mouse, which mirrors the genotype of the human pathology however requires an extended time to manifest symptoms and to be carefully studied. Copyright 2019 The Authors. Published by Elsevier Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_423,

title = {Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations.},

author = {Antoniel M and Traina F and Merlini L and Andrenacci D and Tigani D and Santi S and Cenni V and Sabatelli P and Faldini C and Squarzoni S},

url = {https://www.mdpi.com/2073-4409/9/2/409},

doi = {10.3390/cells9020409},

year  = {2020},

date = {2020-01-01},

journal = {Cells},

volume = {9},

number = {2},

pages = {e409},

abstract = {Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_48,

title = {Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning.},

author = {Pellegrini C and Columbaro M and Schena E and Prencipe S and Andrenacci D and Iozzo P and Angela Guzzardi M and Capanni C and Mattioli E and Loi M and Araujo-Vilar D and Squarzoni S and Cinti S and Morselli P and Giorgetti A and Zanotti L and Gambineri A and Lattanzi G},

url = {https://www.nature.com/articles/s12276-019-0289-0},

doi = {10.1038/s12276-019-0289-0},

year  = {2019},

date = {2019-03-04},

urldate = {2019-03-04},

journal = {Experimental & molecular medicine.},

volume = {51},

number = {8},

pages = {89},

abstract = {Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_71,

title = {Report of a novel ATP7A mutation causing distal motor neuropathy.},

author = {Gualandi F and Sette E and Fortunato F and Bigoni S and De Grandis D and Scotton C and Selvatici R and Neri M and Incensi A and Liguori R and Storbeck M and Karakaya M and Simioni V and Squarzoni S and Timmerman V and Wirth B and Donadio V and Tugnoli V and Ferlini A},

url = {https://www.sciencedirect.com/science/article/pii/S0960896619310995?via%3Dihub},

doi = {10.1016/j.nmd.2019.08.008},

year  = {2019},

date = {2019-03-15},

journal = {Neuromuscular disorders},

volume = {29},

number = {10},

pages = {776-785},

abstract = {We describe a novel ATP7A gene mutation associated with distal motor neuropathy, mild connective tissue abnormalities and autonomic disturbances. Next-generation sequencing analysis of a lower-motor neuron diseases gene panel was performed in two sibs presenting with distal motor neuropathy plus an autonomic dysfunction, which main manifestations were retrograde ejaculation, diarrhea and hyperhydrosis. Probands underwent dysmorphological, neurological, electrophysiological as well as biochemical evaluations and somatic and autonomic innervation studies on skin biopsies. A novel missense mutation (p.A991D) was identified in the X-linked ATP7A gene, segregating in both brothers and inherited from their healthy mother. Biochemical studies on patients' blood samples showed reduced serum copper and ceruloplasmin levels. Clinical and neurophysiological evaluation documented dysautonomic signs. Quantitative evaluation of skin innervation disclosed a small fiber neuropathy with prevalent autonomic involvement. Mutations in the ATP7A gene, encoding for a copper-transporting ATPase, have been associated with the severe infantile neurodegenerative Menkes disease and in its milder variant, the Occipital Horn Syndrome. Only two ATP7A mutations were previously reported as causing, a pure axonal distal motor neuropathy (dHMN-SMAX3). The phenotype we report represents a further example of this rare genotype-phenotype correlation and highlights the possible occurrence in SMAX3 of autonomic disturbances, as described for Menkes disease and Occipital Horn Syndrome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_293,

title = {Barrier-to-Autointegration Factor (BAF) involvement in prelamin A-related chromatin organization changes.},

author = {Loi M and Cenni V and Duchi S and Squarzoni S and {Lopez-Otin C} and Foisner R and Lattanzi G and Capanni C},

url = {http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=6697&pubmed-linkout=1},

doi = {10.18632/oncotarget.6697},

year  = {2016},

date = {2016-03-08},

urldate = {2016-03-08},

journal = {Oncotarget},

volume = {7},

number = {13},

pages = {15662-15677},

abstract = {Chromatin disorganization is one of the major alterations linked to prelamin A processing impairment. In this study we demonstrate that BAF is necessary to modulate prelamin A effects on chromatin structure. We show that when prelamin A and BAF cannot properly interact no prelamin A-dependent effects on chromatin occur; similar to what is observed in human Nestor Guillermo Progeria Syndrome cells harboring a BAF mutation, in HEK293 cells expressing a BAF mutant unable to bind prelamin A, or in siRNA mediated BAF-depleted HEK293 cells expressing prelamin A. BAF is necessary to induce histone trimethyl-H3K9 as well as HP1-alpha and LAP2-alpha nuclear relocalization in response to prelamin A accumulation. These findings are enforced by electron microscopy evaluations showing how the prelamin A-BAF interaction governs overall chromatin organization. Finally, we demonstrate that the LAP2-alpha nuclear localization defect observed in HGPS cells involves the progerin-BAF interaction, thus establishing a functional link between BAF and prelamin A pathological forms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_307,

title = {Collagen VI-NG2 axis in human tendon fibroblasts under conditions mimicking injury response.},

author = {Sardone F and Santi S and Tagliavini F and Traina F and Merlini L and Squarzoni S and Cescon M and Wagener R and Maraldi NM and Bonaldo P and Faldini C and Sabatelli P},

url = {https://www.sciencedirect.com/science/article/pii/S0945053X16300233?via%3Dihub},

doi = {10.1016/j.matbio.2016.02.012},

year  = {2016},

date = {2016-02-17},

journal = {Matrix Biology},

volume = {55},

pages = {90-105},

abstract = {In response to injury, tendon fibroblasts are activated, migrate to the wound, and contribute to tissue repair by producing and organizing the extracellular matrix. Collagen VI is a microfibrillar collagen enriched in the pericellular matrix of tendon fibroblasts with a potential regulatory role in tendon repair mechanism. We investigated the molecular basis of the interaction between collagen VI and the cell membrane both in tissue sections and fibroblast cultures of human tendon, and analyzed the deposition of collagen VI during migration and myofibroblast trans-differentiation, two crucial events for tendon repair. Tendon fibroblast displayed a collagen VI microfibrillar network closely associated with the cell surface. Binding of collagen VI with the cell membrane was mediated by NG2 proteoglycan, as demonstrated by in vitro perturbation of collagen VI-NG2 interaction with a NG2-blocking antibody. Cultures subjected to wound healing scratch assay displayed collagen VI-NG2 complexes at the trailing edge of migrating cells, suggesting a potential role in cell migration. In fact, the addition of a NG2-blocking antibody led to an impairment of cell polarization and delay of wound closure. Similar results were obtained after in vitro perturbation of collagen VI extracellular assembly with the 3C4 anti-collagen VI antibody and in collagen VI-deficient tendon cultures of a Ullrich congenital muscular dystrophy patient carrying mutations in COL6A2 gene. Moreover, in vitro treatment with transforming growth factor beta1 (TGFbeta1) induced a dramatic reduction of NG2 expression, both at protein and mRNA transcript level, and the impairment of collagen VI association with the cell membrane. Instead, collagen VI was still detectable in the extracellular matrix in association with ED-A fibronectin and collagen I, which were strongly induced by TGFbeta1 treatment. Our findings reveal a critical role of the NG2 proteoglycan for the binding of collagen VI to the surface of tendon fibroblasts. By interacting with NG2 proteoglycan and other extracellular matrix proteins, collagen VI regulates fibroblasts behavior and the assembly of tendon matrix, thereby playing a crucial role in tendon repair. Copyright 2016 The Authors. Published by Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_330,

title = {All-trans retinoic acid and rapamycin normalize Hutchinson Gilford progeria fibroblast phenotype.},

author = {Pellegrini C and Columbaro M and Capanni C and {D'Apice MR} and Cavallo C and Murdocca M and Lattanzi G and Squarzoni S},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=4939&pubmed-linkout=1},

doi = {10.18632/oncotarget.4939},

year  = {2015},

date = {2015-03-02},

urldate = {2015-03-02},

journal = {Oncotarget},

volume = {6},

number = {30},

pages = {29914-29928},

abstract = {Hutchinson Gilford progeria syndrome is a fatal disorder characterized by accelerated aging, bone resorption and atherosclerosis, caused by a LMNA mutation which produces progerin, a mutant lamin A precursor. Progeria cells display progerin and prelamin A nuclear accumulation, altered histone methylation pattern, heterochromatin loss, increased DNA damage and cell cycle alterations. Since the LMNA promoter contains a retinoic acid responsive element, we investigated if all-trans retinoic acid administration could lower progerin levels in cultured fibroblasts. We also evaluated the effect of associating rapamycin, which induces autophagic degradation of progerin and prelamin A. We demonstrate that all-trans retinoic acid acts synergistically with low-dosage rapamycin reducing progerin and prelamin A, via transcriptional downregulation associated with protein degradation, and increasing the lamin A to progerin ratio. These effects rescue cell dynamics and cellular proliferation through recovery of DNA damage response factor PARP1 and chromatin-associated nuclear envelope proteins LAP2α and BAF. The combined all-trans retinoic acid-rapamycin treatment is dramatically efficient, highly reproducible, represents a promising new approach in Hutchinson-Gilford Progeria therapy and deserves investigation in ageing-associated disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_375,

title = {Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes.},

author = {Cesarini E and Mozzetta C and Marullo F and Gregoretti F and Gargiulo A and Columbaro M and Cortesi A and Antonelli L and Di Pelino S and Squarzoni S and Palacios D and Zippo A and Bodega B and Oliva G and Lanzuolo C},

url = {https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.201504035},

doi = {10.1083/jcb.201504035},

year  = {2015},

date = {2015-11-09},

journal = {Journal of Cell Biology},

volume = {211},

number = {3},

pages = {533-551},

abstract = {Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors-and how this cross talk influences physiological processes-is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors. 2015 Cesarini et al.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_381,

title = {Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins.},

author = {Evangelisti C and Bernasconi P and Cavalcante P and Cappelletti C and D'Apice MR and Sbraccia P and Novelli G and Prencipe S and Lemma S and Baldini N and Avnet S and Squarzoni S and Martelli AM and Lattanzi G},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=3232&pubmed-linkout=1},

year  = {2015},

date = {2015-04-10},

journal = {Oncotarget},

volume = {6},

number = {10},

pages = {7424-7437},

abstract = {Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RAD001 treatment. Our results unravel an unexpected role of lamin A in TGFbeta 2 regulation and indicate rapamycin analogs and neutralizing antibodies to TGFbeta 2 as new potential therapeutic tools for MADA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}