Collagen V and vascular injury promote lung architectural changes in systemic sclerosis

Parra, Edwin Roger; Aguiar, Armando Costa; Teodoro, Walcy Rosolia; Souza, R De; Yoshinari, Natalino Hajime; Capelozzi, Vera Luíza

doi:10.1111/j.1752-699x.2008.00118.x

Cited by 26 publications

(30 citation statements)

References 23 publications

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“…An imbalance in the equilibrium of iNOS and other isoform (nNOS and eNOS) synthesis and the resulting increased production of NO have been reported to be associated with serious cell damage (28). In the present study, the grades at which greatest endothelial damage occurred were the same as those in which morphological studies from this laboratory have shown evidence of endothelial injury and death (18). In other situations, such as vascular changes associated with endotoxic shock (29), and ischemia-reperfusion injuries (30), endothelial iNOS expression has been associated with endothelial damage mediated by free radicals.…”

Section: Discussionsupporting

confidence: 53%

“…Excessive levels of NO react with superoxides to form peroxynitrite and highly reactive hydroxyl radicals, which in turn result in cell injury and apoptosis (17). As the histopathological changes in the lungs of patients with SSc are consistent with alveolar and vessel cell damage (18-20), we presume that this interaction can be characterized by analyzing the expression of proteins regulating NO synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and the outcome, as well as the relationship between these factors and other clinical data and pulmonary function tests, we studied these markers in 23 SSc-NSIP cases.…”

Section: Introductionmentioning

confidence: 96%

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Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Parra

Aguiar

Silva

et al. 2013

Braz J Med Biol Res

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Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 96%

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Parra

Aguiar

Silva

et al. 2013

Braz J Med Biol Res

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“…Endothelial apoptosis in vascular pathology of SS . COLV is proapoptotic; apoptosis of the endothelium of pulmonary vessels is a unique histological abnormality associated with SS (Parra et al, ). In the lung biopsies of SS patients, the endothelial apoptosis is accompanied by vascular basement membrane disruption and COLV overexpression in the vessel walls, all of which likely contribute to the vascular damage in the pathogenesis of SS.…”

Section: Disease and Fibrosismentioning

confidence: 99%

Type V Collagen in Health, Disease, and Fibrosis

Mak

Png

Lee

2016

The Anatomical Record

137

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Type V collagen (COLV) is a regulatory fibril-forming collagen. It has at least three different molecular isoforms-a1(V) 2 a2(V), a1(V) 3, and a1(V)a2(V)a3(V)-formed by combinations of three different polypeptide a chains-a1(V), a2(V), and a3(V). COL V is a relatively minor collagen of the extracellular matrix (ECM). Morphologically, COLV occurs as heterotypic fibrils with type I collagen (COLI), microfilaments, or 12-nm-thick fibrils. COLV is synthesized in various mesenchymal cells and its gene expression is modulated by TGF-b and growth factors. While resistant to digestion by interstitial collagenases, native and denatured COLV are degraded by metalloproteinases and gelatinases, thereby promoting ECM remodeling. COLV interacts with matrix collagens and structural proteins, conferring structural integrity to tissue scaffolds. It binds matrix macromolecules, modulating cellular behavior, and functions. COLV coassembles with COLI into heterotypic fibrils in the cornea and skin dermis, acting as a dominant regulator of collagen fibrillogenesis. COLV deficiency is associated with loss of corneal transparency and classic EhlersDanlos syndrome, while COLV overexpression is found in cancer, granulation tissue, inflammation, atherosclerosis, and fibrosis of lungs, skin, kidneys, adipose tissue, and liver. COLV isoform containing the a3(V) chain is involved in mediating pancreatic islet cell functions. In the liver, COLV is a minor but regular component of the ECM. Increases in COLV are associated with both early and advanced hepatic fibrosis. The neoepitopes of COLV have been shown to be a useful noninvasive serum biomarker for assessing fibrotic progression and resolution in experimental hepatic fibrosis. COLV is multifunctional in health, disease, and fibrosis. Anat Rec, 299:613-629, 2016. V C 2016 Wiley Periodicals, Inc.Key words: collagen V synthesis and degradation; collagen V deficiency and overexpression; collagen V in disease and fibrosis; collagen V neoepitopes; hepatic fibrosis biomarker

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“…Isto sugeriu o uso da droga como um modelo animal de diabetes e como um tratamento médico para câncer das células beta. Atualmente essa droga tem ampla utilização na indução de diabetes experimental [63][64][65][66]. Em síntese, o comprometimento articular no DM, até o presente momento, foi pouco estudado.…”

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Estudo temporal dos colágenos (I, III, IV e V) e produtos de glicação avançada na sinóvia em modelo experimental de diabetes em ratos

Andrade¹

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Collagen V and vascular injury promote lung architectural changes in systemic sclerosis

Abstract: We conclude that the endothelial apoptosis and vascular collagen V interaction reinforce the vascular pathway in the SSc pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential.

Cited by 26 publications

References 23 publications

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Type V Collagen in Health, Disease, and Fibrosis

Estudo temporal dos colágenos (I, III, IV e V) e produtos de glicação avançada na sinóvia em modelo experimental de diabetes em ratos

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