Function analysis of differentially expressed microRNAs in TGF-β1-induced cardiac fibroblasts differentiation

Function analysis of differentially expressed microRNAs in TGF-β1-induced cardiac fibroblasts differentiation
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TGF-β1 诱导心脏成纤维细胞分化中差异表达 microRNA 的功能分析

DOI:
10.1042/bsr20182048
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发表时间:
2019-10
期刊:
Biosci Rep. 2019 Oct 30;39(10). pii: BSR20182048. doi: 10.1042/BSR20182048.
影响因子:
--
通讯作者:
Zhao X
Zhao X
中科院分区:
其他
文献类型:
--
作者:
Liu S;Ke W;Liu Y;Zhao Z;An L;You X;Yang F;Yang X;Wang G;Zhao X

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摘要背景:心脏成纤维细胞分化在心脏重塑和衰竭中起着关键作用,但其潜在的分子机制仍然知之甚少。microRNAs(miRNAs)是细胞分化过程中重要的调控因子。本研究的目的是筛选参与心脏成纤维细胞分化调控的miRNAs。方法:用转化生长因子-β1(TGF-β1)诱导大鼠心肌成纤维细胞向肌成纤维细胞分化。然后应用小RNA测序来检测差异表达的miRNA。结果:共检测到450个已知的miRNAs,miRDeep 2预测出127个新的miRNAs。DEGseq分析和qRT-PCR证实24个已知的miRNAs在TGF-β1诱导的心脏成纤维细胞中差异表达,其中3个上调miRNAs和21个下调miRNAs。通过米兰达算法预测miRNAs的靶基因后,通路分析显示这些潜在的靶基因参与了钙信号通路、II型糖尿病、谷氨酸能突触通路等。同时,在TGF-β1诱导的心肌成纤维细胞分化过程中,还检测到7个可能的miRNAs差异表达。结论:这些差异表达的miRNAs可能在心肌成纤维细胞分化过程中起重要作用。miRNA表达的改变可能会对心脏纤维化的潜在机制产生新的见解,并为心脏纤维化提供新的基于机制的治疗策略。
Abstract Background: Cardiac fibroblasts differentiation plays a critical role in cardiac remodeling and failure, but the underlying molecular mechanisms are still poorly understood. MicroRNAs (miRNAs) had been identified as important regulators during cell differentiation. The aim of the present study was to screen the miRNAs involved in regulation of cardiac fibroblasts differentiation. Methods: The differentiation of rat cardiac fibroblasts into myofibroblasts was induced by transforming growth factor-β1 (TGF-β1). Small RNA sequencing was then applied to detect the differentially expressed miRNAs. Results: A total of 450 known miRNAs were detected, and 127 putative novel miRNAs were predicted by miRDeep2 analysis. DEGseq analysis and qRT-PCR confirmed that 24 known miRNAs were differentially expressed in TGF-β1-induced cardiac fibroblasts, including three up-regulated miRNAs and 21 down-regulated miRNAs. After miRNAs target genes prediction by miRanda algorithm, pathway analysis showed that these potential target genes were involved in Calcium signaling pathway, Type II diabetes mellitus, and Glutamatergic synapse pathway, etc. Meanwhile, seven putative miRNAs were also detected differentially expressed during TGF-β1-induced cardiac fibroblasts differentiation. Conclusions: These differentially expressed miRNAs might play critical roles in cardiac fibroblasts differentiation. Altered expression of miRNAs may yield new insights into the underlying mechanisms of cardiac fibrosis and provide novel mechanism-based therapeutic strategies for cardiac fibrosis.
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