Aims/hypothesis

MicroRNA-21 has been implicated in diabetic complication, including diabetic cardiomyopathy. However, there is limited information regarding the biological role of the miR-21 passenger strand (miR-21-3p) in diabetic cardiac fibrosis. The aim of this study was to investigate the role of miR-21-3p and its target androgen receptor in STZ-induced diabetic cardiac fibrosis.

Methods

The pathological changes and collagen depositions was analyzed by HE, Sirius Red staining and Masson’s Trichrome Staining. MiR-21-3p, AR, NLRP3, caspase1 and collagen I expression were analyzed by western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, miR one step qRT-PCR, respectively. A luciferase reporter assay was used to verify the interaction between miR-21 and the 3' untranslated region (3'UTR) of AR.

Results

Our results indicated that miR-21-3p level was up-regulated, while AR was decreased in STZ-induced diabetic cardiac fibrosis tissues and cardiac fibroblast. High glucose triggers cardiac fibroblasts pyroptosis and collagen deposition. Gain-of-function and loss-of-function assays demonstrated that miR-21-3p mediated the crucial role in diabetic cardiac fibrosis. Our results show that miR-21-3p bound to the 3'UTR of AR post-transcriptionally repressed its expression. We also found AR, which regulates cardiac fibroblasts pyroptosis and collagen deposition through caspase1 signaling.

Conclusions

/interpretation: Taken together, our study showed that miR-21-3p aggravates STZ-induced diabetic cardiac fibrosis through the caspase1 pathways by suppressing AR expression.

中文翻译：

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MiR-21-3p通过抑制雄激素受体触发糖尿病性心肌纤维化中的心脏成纤维细胞焦化

目的/假设

MicroRNA-21与糖尿病并发症有关，包括糖尿病性心肌病。但是，关于miR-21乘客链（miR-21-3p）在糖尿病性心脏纤维化中的生物学作用的信息有限。本研究的目的是研究miR-21-3p及其靶标雄激素受体在STZ诱导的糖尿病性心肌纤维化中的作用。

方法

通过HE，Sirius Red染色和Masson三色染色分析病理变化和胶原沉积。通过Western印迹，免疫组织化学，免疫荧光，qRT-PCR，miR一步qRT-PCR分析了MiR-21-3p，AR，NLRP3，caspase1和胶原蛋白I的表达。萤光素酶报告基因分析用于验证miR-21与AR的3'非翻译区（3'UTR）之间的相互作用。

结果

我们的结果表明，在STZ诱导的糖尿病性心肌纤维化组织和心脏成纤维细胞中，miR-21-3p水平上调，而AR降低。高血糖会触发心脏成纤维细胞的热解和胶原蛋白沉积。功能获得和功能丧失分析表明，miR-21-3p介导了糖尿病性心肌纤维化的关键作用。我们的结果表明，与AR 3'UTR结合的miR-21-3p在转录后抑制了其表达。我们还发现了AR，它通过caspase1信号调节心脏成纤维细胞的凋亡和胶原沉积。

结论

综合说明，我们的研究表明，miR-21-3p通过抑制AR表达，通过caspase1途径加重了STZ诱导的糖尿病性心肌纤维化。