Role of catechin on collagen type I stability upon oxidation: a NMR approach

WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines, and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared with healthy livers. Regression or therapeutic intervention in mice resulted in decreased hepatic WNT-5A levels paralleled by lower collagen levels. Immunohistochemical analysis showed WNT-5A staining in fibrotic septa colocalizing with desmin staining indicating WNT-5A expression in myofibroblasts. In vitro studies confirmed WNT-5A expression in this cell type and showed that TGF-β significantly enhanced WNT-5A expression in contrast to PDGF-BB and proinflammatory cytokines IL-1β and TNF-α. Additionally, TGF-β induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-β-stimulated myofibroblasts were measured compared with nonsilencing siRNA-treated controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A in vitro and in vivo. IFNγ-treated fibrotic mice showed significantly less WNT-5A expression compared with untreated fibrotic mice. In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. NEW & NOTEWORTHY This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.

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Blockade of hypoxia-reoxygenation-mediated collagen type I expression and MMP activity by overexpression of TGF-β1delivered by AAV in mouse cardiomyocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00488.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. H1833-H1838 ◽

Cited By ~ 21

Author(s):

Chang-Ping Hu ◽

Abhijit Dandapat ◽

Yong Liu ◽

Paul L. Hermonat ◽

Jawahar L. Mehta

Keyword(s):

Cardiac Remodeling ◽

Collagen Type ◽

Transforming Growth Factor ◽

Collagen Type I ◽

Type I ◽

Antioxidant Mechanism ◽

Multifunctional Peptides ◽

Expression And Activity ◽

Hypoxia Reoxygenation

Transforming growth factor (TGF)-β1is one of the most pleiotropic and multifunctional peptides known. While the cardioprotective effect of TGF-β1during ischemia is well known, the specific role of TGF-β1in altering the cardiac remodeling process remains unclear. This study was designed to examine the regulation of hypoxia-reoxygenation-mediated collagen type I expression and activity of matrix metalloproteinases (MMPs) by overexpression of TGF-β1in cultured HL-1 mouse cardiomyocytes. TGF-β1was overexpressed in cardiomyocytes by transfection with adeno-associated virus (AAV)/TGF-β1Latentor with AAV/TGF-β1ACT(active TGF-β1). Twenty-four hours of hypoxia followed by 3 h of reoxygenation (H-R) markedly enhanced (pro)collagen type I expression and activity of MMPs concomitant with an increase in reactive oxygen species (ROS) release and LOX-1 expression. Overexpression of TGF-β1reduced these alterations induced by H-R. TGF-β1overexpression also blocked H-R-mediated p38 and p44/42 MAPK activation. Transfection with AAV/TGF-β1ACTwas superior to that with AAV/TGF-β1Latent. These data for the first time demonstrate that H-R induces signals for cardiac remodeling in cardiomyocytes and TGF-β1can modulate, possibly via antioxidant mechanism, these signals. These findings contribute to further understanding of the role of TGF-β1in the cardiac remodeling process.

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The role of collagen type I α2 polymorphisms: intracranial aneurysms in Koreans

Surgical Neurology ◽

10.1016/j.surneu.2009.02.009 ◽

2009 ◽

Vol 72 (1) ◽

pp. 48-53 ◽

Cited By ~ 8

Author(s):

Sung-Pil Joo ◽

Tae-Sun Kim ◽

Il-Kwon Lee ◽

Jung-Kil Lee ◽

Bo-Ra Seo ◽

...

Keyword(s):

Intracranial Aneurysms ◽

Collagen Type ◽

Collagen Type I ◽

Type I

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Discoidin Domain Receptor 2 regulates AT1 receptor expression in Angiotensin II-stimulated cardiac fibroblasts via fibronectin-dependent Integrin-β1 signalling

10.1101/2021.05.06.442987 ◽

2021 ◽

Author(s):

Allen Sam Titus ◽

Harikrishnan V ◽

Mingyi Wang ◽

Edward G Lakkatta ◽

Shivakumar Kailasam

Keyword(s):

Angiotensin Ii ◽

Collagen Type ◽

Cardiac Fibroblasts ◽

Collagen Type I ◽

Cardiac Fibroblast ◽

Regulatory Role ◽

Type I ◽

Integrin Β1 ◽

Fibronectin Expression

Fibronectin is an extracellular matrix glycoprotein with a regulatory role in fundamental cellular processes. Recent reports on the cardioprotective effect of fibronectin inhibition in a setting of myocardial injury suggest a role for fibronectin in cardiac fibroblast function, which remains largely unexplored. This study probed the molecular basis and functional implications of fibronectin gene expression in cardiac fibroblasts exposed to Angiotensin II, a potent pro-fibrotic factor in the myocardium. Using gene knockdown and over-expression approaches, western blotting and promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates Angiotensin II-stimulated transcriptional up-regulation of fibronectin expression by Yes-activated Protein in cardiac fibroblasts. Further, siRNA-mediated fibronectin knockdown attenuated Angiotensin II-dependent expression of anti-apoptotic cIAP2 and promoted cell death under oxidative stress. Fibronectin was also found to mediate Angiotensin II-stimulated collagen type I expression. Importantly, an obligate role for fibronectin was observed in Angiotensin II-stimulated expression of its receptor, AT1R, which would link ECM signalling and Angiotensin II signalling in cardiac fibroblasts. Moreover, the regulatory role of DDR2-dependent fibronectin expression in Ang II-stimulated cIAP2, collagen type I and AT1R expression was mediated by Integrin-β1-integrin-linked kinase signalling. The pro-survival role of fibronectin in cardiac fibroblasts and its regulatory role in collagen and AT1R expression, downstream of DDR2, could be critical determinants of cardiac fibroblast-mediated wound healing following myocardial injury. Our findings point to a complex mechanism of regulation of cardiac fibroblast function involving two major extracellular matrix proteins, collagen type I and fibronectin, and their receptors, DDR2 and Integrin-β1.

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Nicotine Induces Collagen Type I Expression In Lung: Role Of Fibroblasts And Implications For Tobacco-Related Inflammation

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3015 ◽

2011 ◽

Author(s):

Glenn W. Vicary ◽

Edilson Torres-Gonzalez ◽

Tanmay S. Panchabhai ◽

Jeffrey D. Ritzenthaler ◽

Jesse Roman

Keyword(s):

Collagen Type ◽

Collagen Type I ◽

Type I

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The “central vein sign” in inflammatory demyelination: The role of fibrillar collagen type I

Annals of Neurology ◽

10.1002/ana.25461 ◽

2019 ◽

Vol 85 (6) ◽

pp. 934-942 ◽

Cited By ~ 3

Author(s):

Martina Absinta ◽

Govind Nair ◽

Maria Chiara G. Monaco ◽

Dragan Maric ◽

Nathanael J. Lee ◽

...

Keyword(s):

Collagen Type ◽

Collagen Type I ◽

Central Vein ◽

Type I ◽

Fibrillar Collagen

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Fibrillar Collagen Type I Participates in the Survival and Aggregation of Primary Hepatocytes Cultured on Soft Hydrogels

Biomimetics ◽

10.3390/biomimetics5020030 ◽

2020 ◽

Vol 5 (2) ◽

pp. 30

Author(s):

Nathalia Serna-Márquez ◽

Adriana Rodríguez-Hernández ◽

Marisol Ayala-Reyes ◽

Lorena Omega Martínez-Hernández ◽

Miguel Ángel Peña-Rico ◽

...

Keyword(s):

Actin Cytoskeleton ◽

Cell Biology ◽

Collagen Type ◽

Cell Aggregation ◽

Collagen Type I ◽

Type I ◽

Primary Hepatocytes ◽

Cortical Actin ◽

Fibrillar Collagens

Liver is an essential organ that carries out multiple functions such as glycogen storage, the synthesis of plasma proteins, and the detoxification of xenobiotics. Hepatocytes are the parenchyma that sustain almost all the functions supported by this organ. Hepatocytes and non-parenchymal cells respond to the mechanical alterations that occur in the extracellular matrix (ECM) caused by organogenesis and regenerating processes. Rearrangements of the ECM modify the composition and mechanical properties that result in specific dedifferentiation programs inside the hepatic cells. Quiescent hepatocytes are embedded in the soft ECM, which contains an important concentration of fibrillar collagens in combination with a basement membrane-associated matrix (BM). This work aims to evaluate the role of fibrillar collagens and BM on actin cytoskeleton organization and the function of rat primary hepatocytes cultured on soft elastic polyacrylamide hydrogels (PAA HGs). We used rat tail collagen type I and Matrigel® as references of fibrillar collagens and BM respectively and mixed different percentages of collagen type I in combination with BM. We also used peptides obtained from decellularized liver matrices (dECM). Remarkably, hepatocytes showed a poor adhesion in the absence of collagen on soft PAA HGs. We demonstrated that collagen type I inhibited apoptosis and activated extracellular signal-regulated kinases 1/2 (ERK1/2) in primary hepatocytes cultured on soft hydrogels. Epidermal growth factor (EGF) was not able to rescue cell viability in conjugated BM but affected cell aggregation in soft PAA HGs conjugated with combinations of different proportions of collagen and BM. Interestingly, actin cytoskeleton was localized and preserved close to plasma membrane (cortical actin) and proximal to intercellular ducts (canaliculi-like structures) in soft conditions; however, albumin protein expression was not preserved, even though primary hepatocytes did not remodel their actin cytoskeleton significantly in soft conditions. This investigation highlights the important role of fibrillar collagens on soft hydrogels for the maintenance of survival and aggregation of the hepatocytes. Data suggest evaluating the conditions that allow the establishment of optimal biomimetic environments for physiology and cell biology studies, where the phenotype of primary cells may be preserved for longer periods of time.

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Role of collagen turnover biomarkers in the noninvasive assessment of myocardial fibrosis: an update

Biomarkers in Medicine ◽

10.2217/bmm-2020-0298 ◽

2020 ◽

Vol 14 (13) ◽

pp. 1265-1275

Author(s):

Carina Ureche ◽

Alina-Elena Nedelcu ◽

Radu A Sascău ◽

Cristian Stătescu ◽

Mehmet Kanbay ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Collagen Type ◽

Collagen Type I ◽

High Morbidity ◽

Central Feature ◽

Type I ◽

Matrix Remodeling ◽

Early Implementation ◽

Prognostic Utility

The pro-fibrotic milieu, as the result of the extracellular matrix remodeling, is a central feature in the pathophysiology of heart disease and contributes to its high morbidity and mortality. Fibrosis is a recognized risk factor for development of heart failure and arrythmias and is usually detected by cardiac magnetic resonance or endomyocardial biopsy. Collagen type I and type III are major components of the collagen network, and the assessment of their derived biomarkers could serve as estimate of the myocardial fibrotic content. This review summarizes data from numerous studies in which these biomarkers have proven their diagnostic and prognostic utility, setting the stage for further randomized clinical trials that might translate into early implementation of antifibrotic therapies.

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Role of newly synthesized fibronectin in vascular smooth muscle cell migration on matrix-metalloproteinase-degraded collagen

Biochemical Society Transactions ◽

10.1042/bst0300102 ◽

2002 ◽

Vol 30 (2) ◽

pp. 102-107 ◽

Cited By ~ 4

Author(s):

E. Stringa ◽

D. White ◽

R. S. Tuan ◽

V. Knauper ◽

J. Gavrilovic

Keyword(s):

Smooth Muscle ◽

Matrix Metalloproteinase ◽

Vascular Smooth Muscle ◽

Collagen Type ◽

Collagen Type I ◽

Vascular Lesions ◽

Type I ◽

Smooth Muscle Cell Migration ◽

Cellular Fibronectin

The migration of vascular smooth muscle cells (VSMC) is known to be a key process in the development of a number of vascular lesions, although the precise mechanisms involved have still to be elucidated. In the present study, the production of endogenous fibronectins by VSMC migrating across intact and matrix-metalloproteinase-degraded collagen type I has been explored. Cellular fibronectin seems to play a role in the enhanced migration seen when VSMC are exposed to degraded collagen and platelet-derived growth factor-BB. VSMC were found to synthesize both exon IIIA-containing fibronectin (which predominated) and exon IIIB-containing fibronectin. When these cells were exposed to substrates consisting of recombinant exon IIIA-or exon IIIB-containing fibronectin, rates of migration were not elevated above those seen with undegraded collagen. Endogenous fibronectin production may thus be necessary, but not sufficient, for VSMC migration over degraded collagenous substrates.

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Discoidin Domain Receptor 2 Regulates AT1R Expression in Angiotensin II-Stimulated Cardiac Fibroblasts via Fibronectin-Dependent Integrin-β1 Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms22179343 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9343

Author(s):

Allen Sam Titus ◽

Harikrishnan Venugopal ◽

Mereena George Ushakumary ◽

Mingyi Wang ◽

Randy T. Cowling ◽

...

Keyword(s):

Angiotensin Ii ◽

Collagen Type ◽

Cardiac Fibroblasts ◽

Collagen Type I ◽

Cardiac Fibroblast ◽

Type I ◽

Integrin Β1 ◽

Discoidin Domain Receptor ◽

Discoidin Domain Receptor 2

This study probed the largely unexplored regulation and role of fibronectin in Angiotensin II-stimulated cardiac fibroblasts. Using gene knockdown and overexpression approaches, Western blotting, and promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates Angiotensin II-dependent transcriptional upregulation of fibronectin by Yes-activated Protein in cardiac fibroblasts. Furthermore, siRNA-mediated fibronectin knockdown attenuated Angiotensin II-stimulated expression of collagen type I and anti-apoptotic cIAP2, and enhanced cardiac fibroblast susceptibility to apoptosis. Importantly, an obligate role for fibronectin was observed in Angiotensin II-stimulated expression of AT1R, the Angiotensin II receptor, which would link extracellular matrix (ECM) signaling and Angiotensin II signaling in cardiac fibroblasts. The role of fibronectin in Angiotensin II-stimulated cIAP2, collagen type I, and AT1R expression was mediated by Integrin-β1-integrin-linked kinase signaling. In vivo, we observed modestly reduced basal levels of AT1R in DDR2-null mouse myocardium, which were associated with the previously reported reduction in myocardial Integrin-β1 levels. The role of fibronectin, downstream of DDR2, could be a critical determinant of cardiac fibroblast-mediated wound healing following myocardial injury. In summary, our findings suggest a complex mechanism of regulation of cardiac fibroblast function involving two major ECM proteins, collagen type I and fibronectin, and their receptors, DDR2 and Integrin-β1.

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