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2. Fibroblast involvement in soft connective tissue calcificationIvonne Pasquali Ronchetti, Federica Boraldi, Giulia Annovi, Paolo Cianciulli, Daniela Quaglino, 2013, pregledni znanstveni članek Opis: Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of pseudoxanthoma elasticum (PXE) patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibers and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralization. Ključne besede: fibroblasts, PXE, PXE-likedisorders, elastin, extracellularmatrix, ectopiccalcification, mesenchymal
stromalcells Objavljeno v RUNG: 23.08.2019; Ogledov: 3887; Prenosov: 0 Gradivo ima več datotek! Več... |
3. Matrix Gla Protein and Alkaline Phosphatase Are Differently Modulated in Human Dermal Fibroblasts from PXE Patients and ControlsFederica Boraldi, Giulia Annovi, Cees Vermeer, Leon J. Schurgers, Tommaso Trenti, Roberta Tiozzo, Deanna Guerra, Daniela Quaglino, 2013, izvirni znanstveni članek Ključne besede: Fibroblast, Vitamin K, Elastin calcification, Proteomics Objavljeno v RUNG: 23.08.2019; Ogledov: 4430; Prenosov: 0 Gradivo ima več datotek! Več... |
4. Ectopic calcification in β-thalassemia patients is associated with increased oxidative stress and lower MGP carboxylationFederica Boraldi, Maria Immaculada Garcia Fernandez, Chiara Paolinelli DeVincenzi, Giulia Annovi, Leon J. Schurgers, Cees Vermeer, Paolo Cianciulli, Ivonne Pasquali Ronchetti, Daniela Quaglino, 2013, izvirni znanstveni članek Ključne besede: Elastin
Oxidative stress
Matrix Gla protein
Ectopic calcification
Beta-thalassemia Objavljeno v RUNG: 23.08.2019; Ogledov: 4066; Prenosov: 0 Gradivo ima več datotek! Več... |
5. Heparan Sulfate Affects Elastin Deposition in Fibroblasts Cultured from Donors of Different AgesGiulia Annovi, Federica Boraldi, Pasquale Moscarelli, Deanna Guerra, Roberta Tiozzo, Bruna Parma, Pascal Sommer, Daniela Quaglino, 2012, izvirni znanstveni članek Opis: Heparan sulfate (HS), due to its presence on the cell surface and in the extracellular milieu and its ability to
modulate cell signaling, has a fundamental role in both physiological and pathological conditions. For decades
we have demonstrated the occurrence of interactions between glycosaminoglycans (GAGs) and elastic fibers. In
particular, we have recently shown that HS is present inside elastic fibers and plays a role in the assembly and
stability of elastin coacervates. Elastin represents, within the extracellular matrix, the component most severely
affected during aging, and changes in the synthesis and posttranslational modifications of HS have been described,
possibly influencing cellular behavior and protein interactions. Thus, the present study has investigated,
in two different in vitro experimental models, the role of HS on elastin deposition and assembly. Results
demonstrate that: (1) Biological effects of HS are partly dependent on the physicochemical characteristics of the
GAGs; (2) HS does not affect attachment, viability, and growth of human dermal fibroblasts; (3) HS does not
modify elastin gene expression nor elastin synthesis, but favors a-elastin aggregation and, independently from
the age of donors, elastin assembly; (4) HS significantly increases the expression of fibulin 5, and these effects are
especially evident in fibroblasts isolated from aging donors. These data provide a better understanding of the
biological role of HS and offer new perspectives regarding the possibility of restoring and/or preserving the
elastic component with aging. Ključne besede: Heparan sulfate, Elastin, Fibroblasts Objavljeno v RUNG: 23.08.2019; Ogledov: 3667; Prenosov: 0 Gradivo ima več datotek! Več... |
6. Comparison of ex vivo and in vitro human fibroblast ageing models.Federica Boraldi, Giulia Annovi, Roberta Tiozzo, Pascal Sommer, Daniela Quaglino, 2010, izvirni znanstveni članek Opis: Several studies have analyzed modulation of gene expression during physiological ageing with interesting, but often contradictory results, depending on the model used. In the present report we compare age-related metabolic and synthetic parameters in human dermal fibroblasts (HDF) isolated from young and old subjects (ex vivo ageing model) and cultured from early up to late cumulative population doublings (CPD) (in vitro ageing model) in order to distinguish changes induced in vivo by the aged environment and maintained in vitro, from those associated with cell senescence and progressive CPD. Results demonstrate that fibroblasts from aged donors, already at early CPD, exhibit an impaired redox balance, highlighting the importance of this parameter during ageing, even in the presence of standard environmental conditions, which are considered optimal for cell growth. By contrast, several proteins, as those related to heat shock response, or involved in endoplasmic reticulum and membrane trafficking, appeared differentially expressed only during in vitro ageing, suggesting that, at high CPD, the whole cell machinery becomes permanently altered. Finally, given the importance of the elastic component for a long-lasting connective tissue structural and functional compliance, this study focuses also on elastin and fibulin-5 synthesis and deposition, demonstrating a close relationship between fibulin-5 and ageing. Ključne besede: Ageing
Fibroblast
Connective tissue
Oxidative stress
Protein expression
Elastin Objavljeno v RUNG: 23.08.2019; Ogledov: 4118; Prenosov: 0 Gradivo ima več datotek! Več... |
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8. Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum.Federica Boraldi, Giulia Annovi, Deanna Guerra, Paolinelli Devincenzi Chiara, Garcia Fernandez Maria Immaculada, Fulvio Panico, Giorgio De Santis, Roberta Tiozzo, Ivonne Pasquali Ronchetti, Daniela Quaglino, 2009, izvirni znanstveni članek Opis: Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene; however, the pathogenetic mechanisms leading to elastic fibre calcifications and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. Data shed new light on the pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlight the role of differentially expressed proteins as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations. Ključne besede: Ectopic calcification / Elastin / Fibroblast proteome / MRP6 / PXE Objavljeno v RUNG: 23.08.2019; Ogledov: 4210; Prenosov: 0 Gradivo ima več datotek! Več... |
9. Magnesium Modifies the Structural Features of Enzymatically Mineralized Collagen Gels Affecting the Retraction Capabilities of Human Dermal Fibroblasts Embedded within This 3D SystemFederica Boraldi, Angelica Bartolomeo, Giulia Annovi, Romain Debret, Daniela Quaglino, 2016, izvirni znanstveni članek Ključne besede: collagen type I, alkaline phosphatase, fibroblast, three dimensional gel, morphology, mineralization Objavljeno v RUNG: 23.08.2019; Ogledov: 3703; Prenosov: 0 Gradivo ima več datotek! Več... |
10. Connective tissue and diseases: from morphology to proteomics towards the development of new therapeutic appproachDaniela Quaglino, Federica Boraldi, Giulia Annovi, Deanna Guerra, Ivonne Pasquali Ronchetti, 2009, pregledni znanstveni članek Opis: Connective tissue consists of cells separated by the extracellular matrix, whose composition and amount vary according
to age, to functional requirements, and to the presence of pathologic conditions. Within this non-random
macromolecular assembly, collagens, elastin, proteoglycans and structural glycoproteins are mutually interdependent
and modifications of one component, by extrinsic (environmental) and/or intrinsic (systemic, genetic, age-related)
factors, may have consequences on the tissue as a whole. Since decades, different microscopical techniques have been
applied mainly for diagnostic purposes and for detailed descriptions of changes occurring in cells and in matrix
components. More recently, in order to dissect the molecular complexity of the matrix network, to analyse the
interactions between cells and matrix and to look for modulators of cell phenotype, histomorphologic investigations
have been implemented with proteomic studies that allow to identify possible diagnostic markers, and to better
understand patho-mechanisms enabling the design of novel therapeutic strategies. Therefore, the progressively
expanding, although incomplete, knowledge on connective tissue biology, sheds new light on the pathogenesis of
diseases affecting single molecules (i.e. collagenopathies, mucopolysaccharidoses, elastinopathies) and discloses the
importance of matrix components as fundamental regulators of cell phenotype, in relation, for instance, to the aging
process and/or to cancer development and progression. Few examples will be presented demonstrating the promises of
proteomics as a technique leading to the discovery of new therapies and possibly to the development of individualized
treatments for a better patient care. Ključne besede: pathology, proteomics, fibrosis, rheumatology, cancer Objavljeno v RUNG: 23.08.2019; Ogledov: 3688; Prenosov: 0 Gradivo ima več datotek! Več... |