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

Zhao, Jinqiu; Liang, Han

doi:10.1159/000443703

Cited by 24 publications

(19 citation statements)

References 42 publications

(38 reference statements)

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“…Primary cardiac fibroblasts (CFs) were isolated from 1 to 3-day-old Sprague-Dawley rats purchased from the Experimental Animal Center of Nanjing University of Traditional Chinese Medicine as described previously [31]. CFs were cultured in DMEM containing 10 % fetal bovine serum (FBS), 100 U/ml penicillin, and 100 ug/ml streptomycin at standard culture conditions (37 °C, with 5 % CO2).…”

Section: Methodsmentioning

confidence: 99%

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Yuan

Chen

et al. 2017

Cell Physiol Biochem

185

140

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Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. Methods: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice. First, we explored the expression of miR-21 in the infarcted zone in mice model of MI via RT-qPCR. Next, we examined the effects of TGF-β1 on miR-21 expression in cardiac fibroblasts (CFs). Then, CFs were infected with miR-21 mimics or miR-21 inhibitors to investigate the effects of miR-21 on the process of CFs activation in vitro. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-21. At last, in-vivo study was done to confirm MiR-21 regulated myocardial fibrosis after MI in mice. Results: MiR-21 was up-regulated in the infarcted zone after MI in vivo. TGF-β1 treatment increased miR-21 expression in CFs. Overexpression of miR-21 promoted the effects of TGF-β1-induced activation of CFs, evidenced by increased expression of Col-1, α-SMA and F-actin, whereas inhibition of miR-21 attenuated the process of fibrosis. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that Smad7 is a direct target of miR-21. In addition, in-vivo study revealed that MiR-21 regulated myocardial fibrosis after MI in mice. Conclusion: These findings suggested that miR-21 has a critical role in CF activation and cardiac fibrosis after MI through via TGF-β/Smad7 signaling pathway. Thus, miR-21 promises to be a potential therapy in treatment of cardiac fibrosis after MI.

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Section: Methodsmentioning

confidence: 99%

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Yuan

Chen

et al. 2017

Cell Physiol Biochem

185

140

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“…Whereas, down regulated genes such as KHSRP, TRIM72, MLLT1, C3 and DDIT4 were identified as target genes showing the highest number of integration with miRNAs. Low expression of TRIM72 was responsible for development of cardiovascular diseases [113], but loss of this gene may be linked with progression of CAD. In this network down regulated genes such as KH-type splicing regulatory protein (FUSE binding protein 2) (KHSRP), MLLT1 and DDIT4 along with miRNA such as hsa-mir-548ac, hsa-mir-6890-3p, hsa-mir-5681a, hsa-mir-3135b and hsa-mir-3607-3p were predicted as novel prognostic or diagnostic biomarkers and new therapeutic target in CAD.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis

et al. 2019

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Coronary artery disease (CAD) is a major cause of end-stage cardiac disease. Although profound efforts have been made to illuminate the pathogenesis, the molecular mechanisms of CAD remain to be analyzed. To identify the candidate genes in the advancement of CAD, microarray dataset GSE23766 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and pathway and gene ontology (GO) enrichment analyses were performed. The protein-protein interaction network was constructed and the module analysis was performed using the Biological General Repository for Interaction Datasets (BioGRID) and Cytoscape. Additionally, target genes-miRNA regulatory network and target genes-TF regulatory network were constructed and analyzed. There were 894 DEGs between male human CAD samples and female human CAD samples, including 456 up regulated genes and 438 down regulated genes. Pathway enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the superpathway of steroid hormone biosynthesis, ABC transporters, oxidative ethanol degradation III and Complement and coagulation cascades. Similarly, geneontology enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the forebrain neuron differentiation, filopodium membrane, platelet degranulation and blood microparticle. In the PPI network and modules (up and down regulated), MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74 and VHL were hub genes. In the target genes-miRNA regulatory network and target genes—TF regulatory network (up and down regulated), TAOK1, KHSRP, HSD17B11 and PAH were target genes. In conclusion, the pathway and GO ontology enriched by DEGs may reveal the molecular mechanism of CAD. Its hub and target genes, MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74, VHL, TAOK1, KHSRP, HSD17B11 and PAH were expected to be new targets for CAD. Our finding provided clues for exploring molecular mechanism and developing new prognostics, diagnostic and therapeutic strategies for CAD.

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“…Zhao and Lei [51] found, for the first time, that a reduction in TRIM72 in rat cardiac fibroblasts downregulated the TGF-β1/Smad signaling pathway, thus inhibiting the proliferation and migration of the cardiac fibroblasts, causing subsequent changes in the extent of cardiac fibrosis. Chen et al [52] found that TRIM72 induces fibroblast proliferation and promotes fibroblastto-myofibroblast transition by suppressing the STAT3/ Notch-1 pathway.…”

Section: Color Version Available Onlinementioning

confidence: 99%

Emerging Role of TRIM Family Proteins in Cardiovascular Disease

Zhang

et al. 2020

Cardiology

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Ubiquitination is one of the basic mechanisms of cell protein homeostasis and degradation and is accomplished by 3 enzymes, E1, E2, and E3. Tripartite motif-containing proteins (TRIMs) constitute the largest subfamily of RING E3 ligases, with > 70 current members in humans and mice. These members are involved in multiple biological processes, including growth, differentiation, and apoptosis as well as disease and tumorigenesis. Accumulating evidence has shown that many TRIM proteins are associated with various cardiac processes and pathologies, such as heart development, signal transduction, protein degradation, autophagy mediation, ion channel regulation, congenital heart disease, and cardiomyopathies. In this review, we provide an overview of the TRIM family and discuss its involvement in the regulation of cardiac proteostasis and pathophysiology and its potential therapeutic implications.

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

Cited by 24 publications

References 42 publications

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis

Emerging Role of TRIM Family Proteins in Cardiovascular Disease

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