1. Matrix Gla protein (MGP) is involved in elastic fiber calcification in the dermis of Pseudoxanthoma Elasticum (PXE) patients.Federica Boraldi, Annovi Giulia, Paolinelli Devincenzi Chiara, Schurgers Leon J, Vermeer Cees, Quaglino Daniela, Pasquali Ronchetti Ivonne, Gheduzzi Dealba, 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. Najdeno v: ključnih besedah Povzetek najdenega: ...calcification, dermal fibroblast, elastic fiber, human skin, MGP, pseudoxanthoma elasticum... Ključne besede: calcification, dermal fibroblast, elastic fiber, human skin, MGP, pseudoxanthoma elasticum Objavljeno: 22.07.2019; Ogledov: 2417; Prenosov: 0
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2. Hypoxia influences the cellular cross-talk of human dermal fibroblasts. A proteomic approach.Naldini Antonella, Tiozzo Roberta, Sommer Pascal, Carraro Fabio, Annovi Giulia, Boraldi Federica, Quaglino Daniela, 2007, izvirni znanstveni članek Opis: The ability of cells to respond to changes in oxygen availability is critical for many physiological and pathological processes (i.e. development,
aging, wound healing, hypertension, cancer). Changes in the protein profile of normal human dermal fibroblasts were investigated in vitro after
96 h in 5% CO2 and 21% O2 (pO2=140 mm Hg) or 2% O2 (pO2=14 mm Hg), these parameters representing a mild chronic hypoxic exposure
which fibroblasts may undergo in vivo. The proliferation rate and the protein content were not significantly modified by hypoxia, whereas
proteome analysis demonstrated changes in the expression of 56 proteins. Protein identification was performed by mass spectrometry. Data
demonstrate that human fibroblasts respond to mild hypoxia increasing the expression of hypoxia inducible factor (HIF1a) and of the 150-kDa
oxygen-regulated protein. Other differentially expressed proteins appeared to be related to stress response, transcriptional control, metabolism,
cytoskeleton, matrix remodelling and angiogenesis. Furthermore, some of them, like galectin 1, 40S ribosomal protein SA, N-myc-downstream
regulated gene-1 protein, that have been described in the literature as possible cancer markers, significantly changed their expression also in
normal hypoxic fibroblasts. Interestingly, a bovine fetuin was also identified that appeared significantly less internalised by hypoxic fibroblasts. In
conclusion, results indicate that human dermal fibroblasts respond to an in vitro mild chronic hypoxic exposure by modifying a number of
multifunctional proteins. Furthermore, data highlight the importance of stromal cells in modulating the intercellular cross-talk occurring in
physiological and in pathologic conditions. Najdeno v: ključnih besedah Povzetek najdenega: ...Human fibroblast, Primary cell culture, Hypoxia, Connective tissue, Proteome,... Ključne besede: Human fibroblast, Primary cell culture, Hypoxia, Connective tissue, Proteome, 2D gel electrophoresis, Mass-spectrometry Objavljeno: 22.07.2019; Ogledov: 2454; Prenosov: 0
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3. Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum.Ivonne Pasquali Ronchetti, Roberta Tiozzo, Giorgio De Santis, Fulvio Panico, Garcia Fernandez Maria Immaculada, Paolinelli Devincenzi Chiara, Deanna Guerra, Giulia Annovi, Federica Boraldi, 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. Najdeno v: ključnih besedah Ključne besede: Ectopic calcification / Elastin / Fibroblast proteome / MRP6 / PXE Objavljeno: 23.08.2019; Ogledov: 2453; Prenosov: 0
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4. Comparison of ex vivo and in vitro human fibroblast ageing models.Pascal Sommer, Roberta Tiozzo, Giulia Annovi, Federica Boraldi, 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. Najdeno v: ključnih besedah Ključne besede: Ageing
Fibroblast
Connective tissue
Oxidative stress
Protein expression
Elastin Objavljeno: 23.08.2019; Ogledov: 2371; Prenosov: 0
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5. Matrix Gla Protein and Alkaline Phosphatase Are Differently Modulated in Human Dermal Fibroblasts from PXE Patients and ControlsDeanna Guerra, Roberta Tiozzo, Tommaso Trenti, Leon J. Schurgers, Cees Vermeer, Giulia Annovi, Federica Boraldi, Daniela Quaglino, 2013, izvirni znanstveni članek Najdeno v: ključnih besedah Povzetek najdenega: ... Fibroblast, Vitamin K, Elastin calcification,Proteomics... Ključne besede: Fibroblast, Vitamin K, Elastin calcification, Proteomics Objavljeno: 23.08.2019; Ogledov: 2330; Prenosov: 0
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6. Magnesium Modifies the Structural Features of Enzymatically Mineralized Collagen Gels Affecting the Retraction Capabilities of Human Dermal Fibroblasts Embedded within This 3D SystemRomain Debret, Giulia Annovi, Angelica Bartolomeo, Federica Boraldi, Daniela Quaglino, 2016, izvirni znanstveni članek Najdeno v: ključnih besedah Povzetek najdenega: ...collagen type I, alkaline phosphatase, fibroblast, three dimensional gel,
morphology, mineralization... Ključne besede: collagen type I, alkaline phosphatase, fibroblast, three dimensional gel, morphology, mineralization Objavljeno: 23.08.2019; Ogledov: 2198; Prenosov: 0
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