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.

scholarly journals Antifibrotic cardioprotection of berberine via downregulating myocardial IGF-1 receptor-regulated MMP-2/MMP-9 expression in diabetic rats

2018 ◽  
Vol 315 (4) ◽  
pp. H802-H813 ◽  
Author(s):  
Guohua Li ◽  
Wenjuan Xing ◽  
Min Zhang ◽  
Fenghao Geng ◽  
Hongyan Yang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
High Glucose ◽  
Cardiac Fibrosis ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Diabetic Rats ◽  
Type I ◽  
Antifibrotic Effect

Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Our previous studies have shown that berberine, a natural alkaloid, attenuates cardiac ischemia-reperfusion injury in diabetic rats. The aim of present study was to investigate the effects of long-term berberine treatment on cardiac remodeling in diabetic rats and the underlying mechanisms. Diabetic rats induced by low-dose streptozotocin injection combined with 8 wk of high-fat diet displayed significant cardiac matrix collagen deposition and dysfunction, whereas berberine administration (200 mg·kg−1·day−1, gavage 4 wk) significantly ameliorated cardiac fibrosis and dysfunction and reduced cardiac IGF-1 receptor (IGF-1R) expression in diabetic rats. Interestingly, IGF-1R expression was upregulated in cardiac fibroblasts isolated from diabetic hearts or cultured in high-glucose conditions (30 mM). High glucose treatment or IGF-1R overexpression increased matrix metalloproteinase (MMP)-2/MMP-9 expression, α-smooth muscle actin (α-SMA), and collagen type I expression in cardiac fibroblasts. In contrast, berberine treatment significantly inhibited IGF-1R expression and exerted an antifibrotic effect in high glucose-cultured cardiac fibroblasts, as manifested by decreased MMP-2/MMP-9, α-SMA, and collagen type I expression, whereas IGF-1R siRNA plus berberine treatment did not further enhance this antifibrotic effect compared with berberine treatment alone. Taken together, long-term berberine treatment ameliorates cardiac fibrosis and dysfunction by downregulating IGF-1R expression in cardiac fibroblasts and subsequently reducing MMP-2/MMP-9, α-SMA, and collagen type I expression in diabetic hearts. The findings suggest the therapeutic potential of berberine for diabetic cardiomyopathy associated with cardiac fibrosis. NEW & NOTEWORTHY Berberine downregulated IGF-1 receptor expression and matrix metalloproteinase-2/matrix metalloproteinase-9 levels in cardiac fibroblasts and thus inhibited fibroblast differentiation and collagen overproduction in diabetic hearts, suggesting a novel mechanism for antifibrotic cardioprotection of berberine in type 2 diabetes.

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 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.

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 Effect of a Collagen-Based Compound on Morpho-Functional Properties of Cultured Human Tenocytes

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 246 ◽  
Author(s):  
Filippo Randelli ◽  
Alessandra Menon ◽  
Alessio Giai Via ◽  
Manuel Mazzoleni ◽  
Fabio Sciancalepore ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Collagen Type ◽  
Clinical Investigation ◽  
Pain Syndrome ◽  
Collagen Type I ◽  
Type I ◽  
Mrna Levels ◽  
Collagen Turnover ◽  
And Migration ◽  
Proliferation And Migration

Background: Greater Trochanter Pain Syndrome (GTPS) is the main reason for recalcitrant lateral hip pain. Gluteus medius and minimus tendinopathy plays a key role in this setting. An injectable medical compound containing collagen type I (MD-Tissue, Guna) has been produced with the aim to counteract the physiological and pathological degeneration of tendons. In this study we aimed at characterizing the effect of this medical compound on cultured human gluteal tenocytes, focusing on the collagen turnover pathways, in order to understand how this medical compound could influence tendon biology and healing. Methods: Tenocytes were obtained from gluteal tendon fragments collected in eight patients without any gluteal tendon pathology undergoing total hip replacement through an anterior approach. Cell proliferation and migration were investigated by growth curves and wound healing assay, respectively. The expression of genes and proteins involved in collagen turnover were analysed by real-time PCR, Slot blot and SDS-zymography. Results: Our data show that tenocytes cultured on MD-Tissue, compared to controls, have increased proliferation rate and migration potential. MD-Tissue induced collagen type I (COL-I) secretion and mRNA levels of tissue inhibitor of matrix metalloproteinases (MMP)-1 (TIMP-1). Meanwhile, lysyl hydroxylase 2b and matrix metalloproteinases (MMP)-1 and -2, involved, respectively, in collagen maturation and degradation, were not affected. Conclusions: Considered as a whole, our results suggest that MD-Tissue could induce in tenocytes an anabolic phenotype by stimulating tenocyte proliferation and migration and COL-I synthesis, maturation, and secretion, thus favouring tendon repair. In particular, based on its effect on gluteal tenocytes, MD-Tissue could be effective in the discouraging treatment of GTPS. From now a rigorous clinical investigation is desirable to understand the real clinical potentials of this compound.

Anoxia-Reoxygenation Stimulates Collagen Type-I and MMP-1 Expression in Cardiac Fibroblasts

2004 ◽  
Vol 44 (6) ◽  
pp. 682-687 ◽  
Author(s):  
Kui Chen ◽  
Dayuan Li ◽  
Xingjian Zhang ◽  
Paul L. Hermonat ◽  
Jawahar L. Mehta
Keyword(s):  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I

scholarly journals LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung

2012 ◽  
Vol 303 (9) ◽  
pp. L778-L787 ◽  
Author(s):  
Jennifer J. P. Collins ◽  
Elke Kuypers ◽  
Ilias Nitsos ◽  
J. Jane Pillow ◽  
Graeme R. Polglase ◽  
...  
Keyword(s):  
Lung Development ◽  
Collagen Type ◽  
Fetal Lung ◽  
Collagen Type I ◽  
Late Gestation ◽  
Type I ◽  
Mrna Levels ◽  
Antenatal Corticosteroids ◽  
Shh Signaling ◽  
Lung Structure

Chorioamnionitis and antenatal corticosteroids mature the fetal lung functionally but disrupt late-gestation lung development. Because Sonic Hedgehog (Shh) signaling is a major pathway directing lung development, we hypothesized that chorioamnionitis and antenatal corticosteroids modulated Shh signaling, resulting in an altered fetal lung structure. Time-mated ewes with singleton ovine fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) and/or maternal intramuscular betamethasone 7 and/or 14 days before delivery at 120 days gestational age (GA) (term = 150 days GA). Intra-amniotic LPS exposure decreased Shh mRNA levels and Gli1 protein expression, which was counteracted by both betamethasone pre- or posttreatment. mRNA and protein levels of fibroblast growth factor 10 and bone morphogenetic protein 4, which are important mediators of lung development, increased 2-fold and 3.5-fold, respectively, 14 days after LPS exposure. Both 7-day and 14-day exposure to LPS changed the mRNA levels of elastin ( ELN) and collagen type I alpha 1 (Col1A1) and 2 (Col1A2), which resulted in fewer elastin foci and increased collagen type I deposition in the alveolar septa. Corticosteroid posttreatment prevented the decrease in ELN mRNA and increased elastin foci and decreased collagen type I deposition in the fetal lung. In conclusion, fetal lung exposure to LPS was accompanied by changes in key modulators of lung development resulting in abnormal lung structure. Betamethasone treatment partially prevented the changes in developmental processes and lung structure. This study provides new insights into clinically relevant prenatal exposures and fetal lung development.

Sign in / Sign up

Export Citation Format

Share Document