Angiotensin II stimulates collagen synthesis and expression of collagen type I gene in adult rat cardiac fibroblasts

1994 ◽  
Vol 14 (5) ◽  
pp. 378
Author(s):  
T. Liu ◽  
J. Kyle ◽  
S.A. Jimenez ◽  
R.I. Bashey
Keyword(s):  
Angiotensin Ii ◽  
Collagen Synthesis ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I ◽  
Adult Rat ◽  
I Gene

PPARβ/δ activation inhibits angiotensin II-induced collagen type I expression in rat cardiac fibroblasts

2007 ◽  
Vol 460 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Huijie Zhang ◽  
Rongbiao Pi ◽  
Ruifang Li ◽  
Ping Wang ◽  
Futian Tang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I

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

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.

scholarly journals Angiotensin II Regulation of Collagen Type I Expression in Cardiac Fibroblasts

Hypertension ◽  
2004 ◽  
Vol 44 (5) ◽  
pp. 655-661 ◽  
Author(s):  
Kui Chen ◽  
Jiawei Chen ◽  
Dayuan Li ◽  
Xingjian Zhang ◽  
Jawahar L. Mehta
Keyword(s):  
Angiotensin Ii ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I

scholarly journals Angiotensin II Activates Collagen Type I Gene in the Renal Cortex and Aorta of Transgenic Mice through Interaction with Endothelin and TGF-β

2001 ◽  
Vol 12 (12) ◽  
pp. 2701-2710
Author(s):  
Fadi Fakhouri ◽  
Sandrine Placier ◽  
Raymond Ardaillou ◽  
Jean-Claude Dussaule ◽  
Christos Chatziantoniou
Keyword(s):  
Angiotensin Ii ◽  
Transgenic Mice ◽  
Collagen Type ◽  
Renal Cortex ◽  
Collagen Type I ◽  
Collagen I ◽  
Type I ◽  
Cortical Slices ◽  
I Gene

ABSTRACT. Hypertension is frequently associated with the development of renal vascular fibrosis. This pathophysiologic process is due to the abnormal formation of extracellular matrix proteins, mainly collagen type I. In previous studies, it has been observed that the pharmacologic blockade of angiotensin II (Ang II) or endothelin (ET) blunted the development of glomerulo- and nephroangiosclerosis in nitric oxide-deficient hypertensive animals by inhibiting collagen I gene activation. The purpose of this study was to investigate whether and how AngII interacts with ET to activate the collagen I gene and whether transforming growth factor-β (TGF-β) could be a player in this interaction. Experiments were performedin vivoon transgenic mice harboring the luciferase gene under the control of the collagen I-α2 chain promoter (procolα2[I]). Bolus intravenous administration of AngII or ET produced a rapid, dose-dependent activation of collagen I gene in aorta and renal cortical slices (threefold increase over control at 2 h,P< 0.01). The AngII-induced effect on procolα2(I) was completely inhibited by candesartan (AngII type 1 receptor antagonist) and substantially blunted by bosentan (dual ET receptor antagonist) (P< 0.01), whereas the ET-induced activation of collagen I gene was blocked only by bosentan. In subsequent experiments, TGF-β (also administered intravenously) produced a rapid increase of procolα2(I) in aorta and renal cortical slices (twofold increase over control at 1 h,P< 0.01) that was completely blocked by decorin (scavenger of the active form of TGF-β). In addition, decorin attenuated the activation of collagen I gene produced by AngII (P< 0.01). These data indicate that AngII can activate collagen I gene in aorta and renal cortexin vivoby a mechanism(s) requiring participation and/or cooperation of ET and TGF-β.

scholarly journals Angiotensin II Activates Collagen Type I Gene in the Renal Vasculature of Transgenic Mice During Inhibition of Nitric Oxide Synthesis

Circulation ◽  
1999 ◽  
Vol 100 (18) ◽  
pp. 1901-1908 ◽  
Author(s):  
Jean-Jacques Boffa ◽  
Pierre-Louis Tharaux ◽  
Sandrine Placier ◽  
Raymond Ardaillou ◽  
Jean-Claude Dussaule ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Transgenic Mice ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Nitric Oxide Synthesis ◽  
Renal Vasculature ◽  
I Gene

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

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.

scholarly journals Endothelial cell growth factor and heparin regulate collagen gene expression in keloid fibroblasts

1991 ◽  
Vol 278 (3) ◽  
pp. 863-869 ◽  
Author(s):  
E M L Tan ◽  
J Peltonen
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Collagen Gene ◽  
Endothelial Cell Growth Factor ◽  
Endothelial Cell Growth

Keloids are benign cutaneous tumours characterized by excess deposition of collagen, specifically type I collagen. We report here that collagen biosynthesis, as measured by hydroxyproline synthesis, was markedly inhibited by 65-80% by the combination of endothelial cell growth factor (ECGF) supplement and heparin in keloid fibroblast cultures. Fibroblast cultures that were incubated with ECGF alone also demonstrated a measurable decrease of approx. 50% in collagen synthesis compared with control cultures. The inhibition of collagen synthesis was related to the down-regulation of collagen gene expression. Quantitative measurements of mRNA-cDNA hybrids revealed that the gene expression of collagen type I was decreased by more than 80% by heparin and ECGF. Markedly diminished levels of mRNA encoding collagen type I were also observed in cultures incubated with ECGF alone. The results show that ECGF and heparin elicit a negative regulatory effect on collagen production, and that this inhibition is due largely to the down-regulation of the pro-alpha 1(I) of type I collagen gene. Furthermore, ECGF has a potent suppressive effect, and heparin provides an additive effect to this inhibitory phenomenon.

scholarly journals Effect of ALDH2 on High Glucose-Induced Cardiac Fibroblast Oxidative Stress, Apoptosis, and Fibrosis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoyu Gu ◽  
Tingting Fang ◽  
Pinfang Kang ◽  
Junfeng Hu ◽  
Ying Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
High Glucose ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Cardiac Fibroblast ◽  
Type I ◽  
Mrna Levels ◽  
Neonate Rat

Our study aimed firstly to observe whether ALDH2 was expressed in neonate rat cardiac fibroblasts, then to investigate the effect of activation of ALDH2 on oxidative stress, apoptosis, and fibrosis when cardiac fibroblasts were subjected to high glucose intervention. Cultured cardiac fibroblasts were randomly divided into normal (NG), NG + Alda-1, high glucose (HG), HG + Alda-1, HG + Alda-1 + daidzin, HG + daidzin, and hypertonic groups. Double-label immunofluorescence staining, RT-PCR, and Western blot revealed ALDH2 was expressed in cardiac fibroblasts. Compared with NG, ALDH2 activity and protein expression were reduced, and cardiac fibroblast proliferation, ROS releasing, 4-HNE protein expression, collagen type I and III at mRNA levels, and the apoptosis rate were increased in HG group. While in HG + Alda-1 group, with the increases of ALDH2 activity and protein expression, the cardiac fibroblast proliferation and ROS releasing were decreased, and 4-HNE protein expression, collagen type I and III at mRNA levels, and apoptosis rate were reduced compared with HG group. When treated with daidzin in HG + Alda-1 group, the protective effects were inhibited. Our findings suggested that ALDH2 is expressed in neonate rat cardiac fibroblasts; activation of ALDH2 decreases the HG-induced apoptosis and fibrosis through inhibition of oxidative stress.

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