MicroRNA-34a在心肌纤维化过程中对SH2B3的表达调控

doi:10.6040/j.issn.1671-7554.0.2015.411

摘要/Abstract

摘要： 目的探讨SH2B3在心肌纤维化过程中的表达调控机制。方法体外培养心肌细胞,在接受不同浓度转化生长因子-β1(10、50、100 ng/mL)和不同缺氧时间(3、6、12、24、48 h)处理后,采用Western blotting检测SH2B3蛋白的表达;采用qRT-PCR法检测SH2B3 mRNA和miR-34a的表达;在心肌细胞中转染miR-34a类似物和miR-34a抑制剂后,采用Western blotting法检测SH2B3蛋白的表达;采用荧光素酶报告基因法检测miR-34a对SH2B3基因3'UTR区活性的影响。结果在不同浓度转化生长因子-β1和不同缺氧时间刺激心肌细胞后,SH2B3在mRNA和蛋白的表达水平均降低(P<0.05);miR-34a的表达水平则升高(P<0.05), miR-34a可调控SH2B3的表达(P<0.05); miR-34a通过影响SH2B3 3'UTR活性,调控其表达(P<0.05)。结论 SH2B3在参与成纤维细胞的纤维化过程中受miR-34a的表达调控。

关键词: 心肌纤维化, 转化生长因子-β1, 缺氧, 微小RNA

Abstract: Objective To explore the pathological mechanism of abnormal SH2B3 expression during cardic fibrosis. Methods After H2C9 cells were treated with transformin growth factor-β1(TGF-β1)at different concentrations(10, 50, and 100 ng/mL)and hypoxia stimulation of various duration(3, 6, 12, 24 and 48 h), the expression of SN2B3 protein was detected with Western blotting, and the SN2B3 mRNA and miR-34a expressions were determined with qRT-PCR. After H2C9 cells were transfected with miR-34a mimic/inhibitor, the SH2B3 expression was examined with Western blotting. The effect of miR-34a on the activity of SH2B3 3'UTR was detected with luciferase activity assay. Results After treatment of TGF-β1 and hypoxia, SH2B3 expression decreased at both mRNA and protein levels(P<0.05), but miR-34a expression increased(P<0.05). The miR-34a could regulate SH2B3 expression by directly binding to 3'UTR(P<0.05). Conclusion SH2B3 participates in the fibrosis process of fibroblasts under the regulation of miR-34a.

Key words: Hypoxia, Cardiac fibrosis, Transformin growth factor-β1, MicroRNA

中图分类号:

R542

席福立,张梅. MicroRNA-34a在心肌纤维化过程中对SH2B3的表达调控[J]. 山东大学学报（医学版）, 2016, 54(2): 6-10.

XI Fuli, ZHANG Mei. Regulation of microRNA-34a on SH2B3 expression during cardiac fibrosis[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 6-10.

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