Objective: To investigate the way that miR-136 regulated spleen tyrosine kinase (SYK) and transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathways on renal fibrosis.Methods: 100 male SD (Sprague-Dawley) rats were randomly divided into diabetic nephropathy (DN) group, normal control (NC) group, miR-136 mimics group, and control group. The renal fibrosis model of diabetic rats was established by streptozotocin (STZ) method. NRK-52E cells were transfected into six groups: HG group, HG + miR-136 group, HG + miR-NC group, miR-136 + SYK group, miR-136 + NC group, and control group. Histopathological examination, the expressions of miR-136 and SYK mRNA, the expression of mTOR, blood glucose, urine protein, body weight, creatinine level, blood urea nitrogen (BUN), and KW/BW were detected in each group. Transfection efficiency, the targeted binding, and regulation between miR-136 and SYK, as well as the expression level of related inflammatory factors, the expression levels of SYK, E-Cad (E-cadherin), Vimentin, Collagen I, α-smooth muscle actin (α-SMA), and vascular endothelial growth factor A (VEGFA) were detected.Results: It was shown that the expression level of miR-136 in DN group significantly decreased. The blood glucose and urine protein concentrations in the DN group and miR-136 mimics group significantly increased and the body weight was decreased, but the blood glucose concentration in the miR-136 mimics group increased with time. The prolongation of the decline significantly decreased, and the growth rate of urinary protein reduced. Creatinine, BUN, and the kidney weight to body weight ratio (KW/BW) in DN group increased significantly. Cell culture results showed that SYK was a target gene of miR-136 and miR-136/SYK-mediated renal fibrosis by activating TGF-β1/Smad3 signal.Conclusion: SYK activates TGF-β1/Smad3 signaling, while miR-136 inhibits TGF-β1/Smad3 signaling mediating tubular epithelial cell fibrosis by down-regulating SYK.

中文翻译：

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miR-136通过降低酪氨酸激酶SYK的表达并抑制TGF-β1/ Smad3信号通路来改善糖尿病大鼠的肾纤维化。

目的：探讨miR-136调节脾酪氨酸激酶（SYK）和转化生长因子-β1（TGF-β1）/ Smad3信号通路在肾纤维化中的作用。方法：随机分为100只雄性SD（Sprague-Dawley）大鼠。分为糖尿病肾病（DN）组，正常对照组（NC）组，miR-136模拟组和对照组。采用链脲佐菌素（STZ）法建立糖尿病大鼠肾纤维化模型。将NRK-52E细胞转染为六组：HG组，HG + miR-136组，HG + miR-NC组，miR-136 + SYK组，miR-136 + NC组和对照组。每组均进行组织病理学检查，miR-136和SYK mRNA的表达，mTOR，血糖，尿蛋白，体重，肌酐水平，血尿素氮（BUN）和KW / BW的表达。转染效率，靶向结合，miR-136和SYK之间的调控，相关炎症因子的表达水平，SYK，E-Cad（E-钙黏着蛋白），波形蛋白，胶原I，α-平滑肌肌动蛋白（α-SMA）的表达水平结果：DN组miR-136的表达水平明显降低。DN组和miR-136模拟组的血糖和尿蛋白浓度显着升高，体重减轻，但miR-136模拟组的血糖浓度随时间升高。下降的持续时间明显减少，尿蛋白的生长速率降低。DN组的肌酐，BUN和肾脏的体重比（KW / BW）显着增加。