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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: 3869; Prenosov: 0
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3. 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: 4035; Prenosov: 0
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4. 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: 4193; Prenosov: 0
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5. 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: 3665; Prenosov: 0
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6. Matrix Gla protein (MGP) is involved in elastic fiber calcification in the dermis of Pseudoxanthoma Elasticum (PXE) patients.Gheduzzi Dealba, Federica Boraldi, Annovi Giulia, Paolinelli Devincenzi Chiara, Schurgers Leon J, Vermeer Cees, Quaglino Daniela, Pasquali Ronchetti Ivonne, 2007, izvirni znanstveni članek Opis: Mature MGP (Matrix g-carboxyglutamic acid protein) is known to inhibit soft connective tissues calcification. We
investigated its possible involvement in pseudoxanthoma elasticum (PXE), a genetic disorder whose clinical manifestations
are due to mineralization of elastic fibers. PXE patients have lower serum concentration of total MGP compared to
controls (Po0.001). Antibodies specific for the noncarboxylated (Glu-MGP) and for the g-carboxylated (Gla-MGP) forms of
MGP were assayed on ultrathin sections of dermis from controls and PXE patients. Normal elastic fibers in controls and
patients were slightly positive for both forms of MGP, whereas Gla-MGP was more abundant within control’s than within
patient’s elastic fibers (Po0.001). In patients’ calcified elastic fibers, Glu-MGP intensively colocalized with mineral
precipitates, whereas Gla-MGP precisely localized at the mineralization front. Data suggest that MGP is present within
elastic fibers and is associated with calcification of dermal elastic fibers in PXE.
Ključne besede: calcification, dermal fibroblast, elastic fiber, human skin, MGP, pseudoxanthoma elasticum
Objavljeno v RUNG: 22.07.2019; Ogledov: 4190; Prenosov: 0
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