Abstract 370: MicroRNA-19b Contributes to Cardiac Fibrosis

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Ping Chen ◽  
Dongchao Lv ◽  
Jiahong Xu ◽  
Qiulian Zhou ◽  
Qi Sun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Suppressor Gene ◽  
Tissue Growth ◽  
Neonatal Rat ◽  
Cell Counting ◽  
Mrna Levels ◽  
And Migration ◽  
Proliferation And Migration

Fibrosis is one of the most important characteristics of cardiac remodeling during heart failure. The accumulation of extracellular matrix (ECM) within myocardium is the major feature of cardiac fibrosis. microRNA (miR)-19b, a key functional member of miR-19-72 cluster family, has been suggested to be involved in aging-induced heart failure through regulating ECM-related proteins, such as connective tissue growth factor (CTGF), thrombospondin-1 (TSP-1), collagen-1A1, and collagen-3A1. In the current study, we aimed to investigate the role of miR-19b in cardiac fibroblast function and ECM production using neonatal rat cardiac fibroblasts in primary culture. We found that overexpression of miR-19b increased, while inhibition of miR-19b decreased the proliferation and migration of cardiac fibroblasts, using Cell Counting Kit-8 (CCK-8) (0.660±0.019 vs 0.720±0.014 in nc-mimic and miR-19b mimic, 0.506±0.009 vs 0.454±0.008 in nc-inhibitor and miR-19b inhibitor, respectively), EdU incorporation assay (0.059±0.002 vs 0.096±0.006 in nc-mimic and miR-19b mimic, 0.059±0.006 vs 0.040±0.003 in nc-inhibitor and miR-19b inhibitor, respectively), and wound healing assay (0.528±0.024 vs 0.896±0.027 in nc-mimic and miR-19b mimic,0.520±0.028 vs 0.174±0.019 in nc-inhibitor and miR-19b inhibitor, respectively), respectively. Meanwhile, the inhibition of miR-19b downregulated the mRNA levels of α-SMA (0.556±0.048 vs 1.038±0.137 in nc-inhibitor and miR-19b inhibitor, respectively) and collagen-1 (1.023±0.116 vs 0.551±0.033 in nc-inhibitor and miR-19b inhibitor, respectively) in cardiac fibroblasts, indicating a reduction in fibroblast activation and ECM production via miR-19b inhibition. Furthermore, we found that PTEN was negatively regulated by miR-19b in cardiac fibroblasts using western blot analysis. PTEN, a well-known tumor-suppressor gene, has been known to inhibit cell proliferation and migration. However, it remains to be further clarified whether PTEN could mediate the effect of miR-19b in the proliferation, migration and activation of fibroblasts. These data might provide important evidence suggesting that miR-19b could be a potential therapeutic target for cardiac fibrosis.

scholarly journals Tripartite Motif Protein 72 Regulates the Proliferation and Migration of Rat Cardiac Fibroblasts via the Transforming Growth Factor-β Signaling Pathway

Cardiology ◽  
2016 ◽  
Vol 134 (3) ◽  
pp. 340-346 ◽  
Author(s):  
Jianquan Zhao ◽  
Han Lei
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Neonatal Rat ◽  
Tripartite Motif ◽  
Tripartite Motif Protein ◽  
And Migration ◽  
Proliferation And Migration

Background: The proliferation and migration of cardiac fibroblasts are critical for the progress of cardiac fibrosis. Tripartite motif protein 72 (Trim72), also known as MG53, mediates the dynamic process of membrane fusion and exocytosis in striated muscle. However, the role of Trim72 in the proliferation and migration of cardiac fibroblasts is unknown. Methods: In the present study, we used small interference RNA (siRNA) to silence Trim72 and then investigated the effects of Trim72 on cardiac fibroblast proliferation and migration, which were activated during cardiac remodeling after myocardial infarction. Cardiac fibroblasts were isolated from 2- to 3-day-old neonatal Sprague-Dawley rats and transfected with siRNA. A cell-counting assay was used to determine the proliferation of cardiac fibroblasts. A Boyden chamber assay was performed to determine the migration of cardiac fibroblasts. Results: Our study has, for the first time, demonstrated that Trim72 regulates the cell proliferation and migration of rat cardiac fibroblasts. Furthermore, the data from the gene expression profile microarray analysis indicate that Trim72 depletion can cause downregulation of the transforming growth factor (TGF)-β signaling pathway, suggesting that Trim72 regulates the proliferation and migration of cardiac fibroblasts probably via the TGF-β signaling pathway. Conclusions: We have demonstrated that Trim72 might play a pivotal role in the proliferation of neonatal rat cardiac fibroblasts, which could be a potential target for the treatment of cardiac fibrosis. However, the involvement of other signaling pathways and factors in the formation of cardiac fibrosis cannot be excluded.

Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 91-99 ◽  
Author(s):  
Yang Xiao ◽  
Wei Chang ◽  
Qing-Qing Wu ◽  
Xiao-Han Jiang ◽  
Ming-Xia Duan ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Mammalian Target Of Rapamycin ◽  
Transforming Growth Factor Β1 ◽  
Neonatal Rat ◽  
Cell Counting ◽  
Compound C ◽  
Underlying Mechanisms

AbstractFibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of aucubin. As a result, aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.

Abstract 13837: Adrenergic Receptors β2 and β3 Transduce Differential Signals in Cardiac Fibroblasts

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kota Tonegawa ◽  
Hiroyuki Nakayama ◽  
Hiromi Igarashi ◽  
Sachi Matsunami ◽  
Nao Hayamizu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Cell Types ◽  
Neonatal Rat ◽  
Rt Pcr ◽  
Β Blocker ◽  
Selective Agonists ◽  
Selective Blocker ◽  
Camkii Activation

Background: Cardiac fibroblasts (CFs) are the most prevalent cell types in heart and play important roles in cardiac remodeling. While the roles of β-adrenergic receptor (βAR) signaling in cardiomyocytes (CMs) are well characterized, those in CFs remain to be elusive due to lack of convenient method to assess those signaling. There are three subtypes of, βAR β1, β2, β3 and β2AR is reported to be expressed in CFs by which enhances cell proliferation and production of inflammatory cytokines. Clinical efficacy of non-selective β blocker carvedilol for heart failure (HF) surpasses that of β1 selective blocker metoprolol, suggesting critical roles of β2 and β3AR in the pathogenesis of HF. Objective: To elucidate the signaling downstream βARs in CFs in heart. Methods and Results: Caveolae is an important microdomain for signal transduction, such as βAR, present in CMs or CFs. To elucidate βAR signaling of caveolae in CFs, we generated a fusion protein composed of phospholamban (PLN) and caveolin3 (Cav3) representing PKA activation as phosphorylation at S16 of PLN and CaMKII as that at T17 in caveolae. Thus, activation of PKA or CaMKII is detectable by anti-phospho-S16 or T17 antibody, respectively. In neonatal rat CFs (NRCFs) infected PLN-Cav3 adenovirus, stimulation by isoproterenol (ISO) led to enhanced phosphorylation of both S16 and T17, suggesting PKA and CaMKII activation in caveolae of CFs. RT-PCR analyses showed β2AR and β3AR were present in NRCFs. Stimulation with β2AR selective agonists activated both PKA and CaMKII, while β3AR elicited solely PKA activation, analyzed by using β3AR selective agonist/antagonist. In addition, in order to examine the significance of βAR stimulation for heart failure, we administered ISO continuously for two weeks in β2ARKO mice. As a result, fibrosis was suppressed in β2ARKO mice compared with wild-type mice (0.35% vs 2.37%, p<0.05) suggesting critical roles of β2AR in development of cardiac fibrosis caused by βAR stimulation in mice. Conclusions: Both β2 and β3AR are expressed in NRCFs and transduce distinct signaling and β2AR selective stimulation elicit development of cardiac fibrosis via activation of CaMKII signaling. Thus, selective βAR regulation could be potential novel anti-fibrotic therapeutics in HF.

scholarly journals MiR-486-5p Suppresses Proliferation and Migration of Hepatocellular Carcinoma Cells through Downregulation of the E3 Ubiquitin Ligase CBL

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Jia He ◽  
Bin Xiao ◽  
Xiaoyan Li ◽  
Yongyin He ◽  
Linhai Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Ubiquitin Ligase ◽  
Target Genes ◽  
E3 Ubiquitin Ligase ◽  
Tumor Stage ◽  
Suppressor Gene ◽  
Cell Counting ◽  
And Migration ◽  
Proliferation And Migration

MicroRNAs have been broadly implicated in cancer, but precise functions and mechanisms in carcinogenesis vary among cancer types and in many cases remain poorly understood. Hepatocellular carcinoma (HCC) is among the most frequent and lethal cancers. The aim of the present study was to investigate the role of miR-486-5p in HCC and identify its specific target. MiR-486-5p was significantly downregulated in HCC tissues and cell lines compared with noncancerous tissues and, respectively, although expression level was not correlated with the degree of infiltration or tumor stage. However, miR-486-5p overexpression in HCC cells inhibited proliferation and migration as evidenced by CCK-8 cell counting, wound healing, and transwell assays, indicating that miR-486-5p is an HCC suppressor. We employed four miRNA databases to predict the target genes of miR-486-5p and verified retrieved genes using qPCR and western blotting. The E3 ubiquitin ligase CBL was significantly downregulated by miR-486-5p overexpression in HCC cell lines at both mRNA and protein level, and overexpression of CBL counteracted the inhibitory effects of miR-486-5p on HCC cell proliferation and migration. Moreover, CBL expression was negatively correlated with miR-486-5p expression in HCC tissues. Collectively, our results suggest that miR-486-5p may act as a tumor suppressor gene in HCC by downregulating CBL expression.

scholarly journals Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Gao ◽  
Longfei Liu ◽  
Zhuolin Li ◽  
Yingxian Pang ◽  
Jiaqi Shi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Collagen Type ◽  
Tissue Growth ◽  
Cell Counting ◽  
Type I ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Pheochromocytoma, as a neuroendocrine tumor with the highest genetic correlation in all types of tumors, has attracted extensive attention. Von Hipper Lindau (VHL) has the highest mutation frequency among the genes associated with pheochromocytoma. However, the effect of VHL on the proteome of pheochromocytoma remains to be explored. In this study, the VHL knockdown (VHL-KD) PC12 cell model was established by RNA interference (shRNA). We compared the proteomics of VHL-KD and VHL-WT PC12 cell lines. The results showed that the expression of 434 proteins (VHL shRNA/WT &gt; 1.3) changed significantly in VHL-KD-PC12 cells. Among the 434 kinds of proteins, 83 were involved in cell proliferation, cell cycle and cell migration, and so on. More importantly, among these proteins, we found seven novel key genes, including Connective Tissue Growth Factor (CTGF), Syndecan Binding Protein (SDCBP), Cysteine Rich Protein 61 (CYR61/CCN1), Collagen Type III Alpha 1 Chain (COL3A1), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type V Alpha 2 Chain (COL5A2), and Serpin Family E Member 1 (SERPINE1), were overexpressed and simultaneously regulated cell proliferation and migration in VHL-KD PC12 cells. Furthermore, the abnormal accumulation of HIF2α caused by VHL-KD significantly increased the expression of these seven genes during hypoxia. Moreover, cell-counting, scratch, and transwell assays demonstrated that VHL-KD could promote cell proliferation and migration, and changed cell morphology. These findings indicated that inhibition of VHL expression could promote the development of pheochromocytoma by activating the expression of cell proliferation and migration associated genes.

Abstract 272: The Orphan Receptor GPRC5B Increases Pro-Inflammatory Signaling in Neonatal Rat Cardiac Fibroblasts and Cardiac MMP-9-expression in vivo

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Friedrich A von Samson-Himmelstjerna ◽  
Greta Freundt ◽  
Norbert Frey ◽  
Hans-Joerg Hippe
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Orphan Receptor ◽  
Neonatal Rat ◽  
Myocardial Inflammation ◽  
Mouse Heart ◽  
Mrna Levels ◽  
Protein Levels ◽  
Cellular Inflammatory Response ◽  
The Impact

Background: Inflammatory processes driven by cardiac fibroblasts (CF) play a major role in cardiac fibrosis and eventually diastolic dysfunction leading to heart failure. GPRC5B, a novel G protein-coupled orphan receptor, is involved in inflammatory pathways in adipocytes and endogenously expressed in CF. Hypothesis: We assessed the impact of GPRC5B on inflammatory and fibrotic pathways in isolated neonatal rat CF and mouse heart. Methods & Results: We show that 48h-stimulation of CF with Tumor Necrosis Factor α (TNFα, 50ng/ml) or Lipopolysaccharides (LPS, 100ng/ml) leads to a significant up-regulation of GPRC5B protein levels compared to unstimulated cells (TNFα +74%, p<0.01; LPS +111%, p<0.001, n=8) . This is confirmed by evaluation of mRNA levels after 12h-stimulation ( TNFα +69%, p<0.01; LPS +61%, p<0.01, n=9) . Similarly, a mechanical stretch of 18% of CF length for 24h increases GPRC5B-mRNA by 83% (p<0.01, n=6). Adenoviral overexpression of GPRC5B results in an increased TNFα- ( +84%, p<0.01) , Interleukin 1ß- (IL1ß, +56%, p<0.05 ), Interleukin 6- (IL6, +32%, p<0.05 ) and Matrix-Metalloproteinase 9- (MMP9, +133%, p<0.01 ) mRNA production in CF ( AdLacZ vs. AdGPRC5B, n=9) . After an additional 24h-stimulation with LPS (10ng/ml), IL1ß-, IL6- and MMP9-mRNA increases as compared to AdLacZ-infected control cells ( AdLacZ+LPS vs. AdGPRC5B+LPS : IL1ß +114%, p<0.01; IL6 +113%, p<0.05; MMP9 +195%, p<0.01; n=8). Conversely, siRNA mediated knockdown to 25% of endogenous protein levels followed by 24h-stimulation with LPS (10ng/ml) lowers significantly the expression of TNFα-, IL1ß- and IL6-mRNA when compared to control-transfected cells (siNeg+LPS vs. siGPRC5B+LPS: TNFα -28%, p<0.05; IL1ß -30%, p<0.05; MMP9 -34%, p<0.05; n=8). These findings are supported by Western Blot analysis of heart tissue from GPRC5B-transgenic mice revealing an increased protein expression of MMP9 in contrast to wild type mice (WT vs. GPRC5B-TG: MMP9 +60%, p<0.001; n=10). Conclusion: GPRC5B is up-regulated in cardiac models of inflammation and mechanical stress. GPRC5B modulates cellular inflammatory response by increasing the levels of key cytokines in CF and of MMP9 expression in mouse heart pointing to a role in myocardial inflammation and cardiac remodeling.

scholarly journals Targeting YOD1 by RNA Interference Inhibits Proliferation and Migration of Human Oral Keratinocytes through Transforming Growth Factor-β3 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Long Zhou ◽  
Gang Chen ◽  
Meng-Xue Li ◽  
Heng-Xue Wang ◽  
Jia-Wei Hong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Rna Interference ◽  
Transforming Growth Factor ◽  
Cell Counting ◽  
Mrna Levels ◽  
Oral Keratinocytes ◽  
Protein Levels ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Objective. We have identified a gene YOD1 encoding deubiquitinating enzyme (DUB) responsible for nonsyndromic cleft lip with or without cleft palate (NSCL/P). We aimed to determine the effects of YOD1 RNA interference (RNAi) on cell proliferation and migration, playing an important role in lip and palate formation, and to clarify whether the mechanisms involved TGF-β3 signaling associated with NSCL/P. Methods. RNAi was applied to construct vectors expressing YOD1 small interference RNAs (siRNAs). The vectors were transfected into the human oral keratinocytes (HOK) cells. The cell proliferation and migration were evaluated by the cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The mRNA levels were detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The protein levels were investigated by western blotting. Results. The proliferation of YOD1 siRNA-transfected HOK cells was remarkably inhibited. The migration rate was significantly decreased in the YOD1 siRNA-transfected HOK cells. The TGF-β3 mRNA and protein levels were decreased significantly by siRNA-mediated knockdown of YOD1. YOD1 RNAi reduced the phosphor-Smad2/3 levels significantly. Conclusions. YOD1 RNAi may inhibit cell proliferation and migration associated with the pathogenesis of NSCL/P through TGF-β3 signaling. The study indicates a novel role of YOD1 in regulating TGF-β3 signaling to affect cell proliferation and migration resulting in NSCL/P.

scholarly journals Overexpression of Calreticulin Promotes Cardiac Fibroblasts Activation Via Regulating IRE1 Pathway

2021 ◽  
Author(s):  
liu zhiyue ◽  
Zhiyue Liu ◽  
Wen Zhang ◽  
Junli Li ◽  
Lei Xiao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
High Titer ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Migration Rates ◽  
And Migration ◽  
Proliferation And Migration

Abstract Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone involved in cardiac fibroblasts (CFs) activation. It has been reported that the expression of CRT increased in the process of CFs activation. However, the role of CRT in CFs activation and the mechanism is not yet fully elucidated. Therefore, we aimed to verify whether CRT was involved in CFs activation and the possible mechanism underlying this process. We found that CRT protein level was elevated in AngⅡ-induced CFs activation. Knocking down CRT by its siRNA could decrease the protein expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β), and meanwhile attenuate proliferation and migration ratio of CFs. Moreover, the proliferation and migration rates of CFs were promoted and the expression of CTGF, α-SMA and TGF-β were increased when transfection with high-titer adenovirus of CRT. In AngⅡ-induced CFs, inositol-requiring enzyme 1(IRE-1), one of the main ER pathways, was inhibited through CRT silence and activated through CRT overexpression. Overall, this study demonstrates that CRT overexpression could promote AngⅡ induced-CFs activation by activating IRE1 pathway, which could be a potential target for CFs activation.

Abstract 304: Estrogen Plays a Protective Role in Advanced Heart Failure by Suppressing Cardiac Fibrosis Associated Genes via miR129 Induction

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Salil Sharma ◽  
Andrea Iorga ◽  
Harnek Singh ◽  
Jingyaun Li ◽  
Mansoureh Eghbali
Keyword(s):  
Heart Failure ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Fibroblast Proliferation ◽  
Short Term ◽  
Short Term Treatment

We have previously shown that short term treatment of estrogen(E2) can rescue advance heart failure(HF) and decreases associated fibrosis. We hypothesized that E2 can reduce fibrosis by regulating the levels of specific microRNAs including miR129-5p(miR129) through ERβ mediated mechanism. We used transaortic constriction to induce HF in male mice, and once the ejection fraction (EF) reached ~30%, one group of animals was sacrificed (HF), and the other group received 17b-estradiol via a subcutaneous pellet implant (0.012mg/pellet, n=16) (E2) for 10 days. Sham-operated mice served as CTRL. Serial echocardiography was performed to monitor cardiac structure and function. Short-term E2 treatment rescued pressure overload-induced decompensated HF in mice by restoring the EF from 33.17±1.12% to 53.05±1.29 (p <0.001, n=16). E2 decreased both interstitial and perivascular fibrosis in HF. Microarray analysis comparing HF with E2 revealed ~70 microRNAs including miR129 regulated by E2. qPCR validation revealed that E2 treatment upregulates miR129 by 2 folds compared to HF restoring it to CTRL levels. Treatment of HF with ERβ agonist (DPN), but not ERα agonist (PPT) resulted in the upregulation of miR129 indicating the E2 mediated induction of miR129 is mediated through ERβ. In vitro, angiotensin II treatment significantly downregulated miR129 expression in neonatal rat fibroblasts (NRVF) which was restored by E2 and DPN but not by E2+ERβ antagonist (PHPT) further confirming the role of ERβ in regulating miR129. In vitro, OE of miR129 in both neonatal and adult rat cardiac fibroblasts (ARVF) resulted in significant downregulation of transcripts of many in-silico predicted pro-fibrotic target genes including EGFR, RUNX, GREM1, COL2A, PDGFA, PDGFRA and the transcription factor SOX4. OE of miR129 in fibroblasts also resulted in downregulation of EGFR protein. Gain of miR129 prevented the transition of fibroblasts to myofibroblasts in both NRVF and ARVF and inhibited fibroblast proliferation in vitro. In conclusion, E2 treatment during HF induces miR129 likely through ERβ. MiR129 represses fibrosis by targeting key genes associated with cardiac fibrosis, inhibits fibroblast proliferation and fibroblast to myofibroblast transition.

scholarly journals miR-29b-3p inhibits post-infarct cardiac fibrosis by targeting FOS

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Yongliang Xue ◽  
Xuefang Fan ◽  
Ruobing Yang ◽  
Yuanyuan Jiao ◽  
Yang Li
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Cell Counting ◽  
Migration Ability ◽  
Western Blot Assay ◽  
Collagen Iii ◽  
Elevated Expression ◽  
Rna Immunoprecipitation ◽  
And Migration ◽  
Tgf Β1

Abstract Background: Cardiac fibrosis after myocardial infarction (MI) is a major cause of heart deterioration. Recently, the roles of microRNAs (miRNAs) in various cardiovascular diseases associated with cardiac fibrosis have been extensively investigated. The present study aimed to investigate the role and mechanism of miR-29b-3p in cardiac fibrosis after MI. Methods: miR-29b-3p expression in TGF-β1-activated cardiac fibroblasts (CFs) was detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) and Trans-well assays were performed to evaluate CFs proliferation and migration ability, respectively. Protein expressions of α-SMA, collagen I, collagen III, MMP2, and MMP9 were examined by Western blot assay. Bioinformatics, luciferase, and RNA immunoprecipitation (RIP) assays were carried out to determine whether FOS was targeted by miR-29b-3p. Results: TGF-β1 treatment dose-dependently curbed miR-29b-3p expression in CFs. miR-29b-3p restrained the promotive impacts of TGF-β1 on CFs proliferation, migration, and differentiation. FOS was affirmed to be a target of miR-29b-3p, elevated expression of FOS reversed the inhibitory effects of miR-29b-3p on cell proliferation, migration, and differentiation in TGF-β1-activated CFs. Conclusion: miR-29b-3p degraded the pro-fibrosis effect induced by TGF-β1 via targeting FOS, providing a prospective therapeutic avenue for cardiac fibrosis after MI.

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