Tongxinluo ameliorates renal structure and function by regulating miR-21-induced epithelial-to-mesenchymal transition in diabetic nephropathy.
Tongxinluo ameliorates renal structure and function by regulating miR-21-induced epithelial-to-mesenchymal transition in diabetic nephropathy.
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DOI：
10.1152/ajprenal.00528.2013
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发表时间：
2014-03
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通讯作者：
Jin-yang Wang;Yanbin Gao;N. Zhang;Dawei Zou;Li-ping Xu;Zhiyao Zhu;Jiao-yang Li;Sheng-nan Zhou;Fang-qiang Cui;Xiang-jun Zeng;Jian Geng;Jinkui Yang
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作者：
Jin-yang Wang;Yanbin Gao;N. Zhang;Dawei Zou;Li-ping Xu;Zhiyao Zhu;Jiao-yang Li;Sheng-nan Zhou;Fang-qiang Cui;Xiang-jun Zeng;Jian Geng;Jinkui Yang
糖尿病肾病（DN）是糖尿病最重要的微血管病变之一。上皮-间质转化（epithelial-to-mesenchymal transition， EMT）在DN中起重要作用。microRNA-21 （miR-21）的生理作用与EMT密切相关。然而，通心络（TXL）是否通过调节mir -21诱导的DN中EMT来改善肾脏结构和功能尚不明确。本研究旨在确定TXL对miR-21诱导的肾小管EMT的影响，并探讨miR-21与TGF-β1/smads信号的关系。分别采用实时荧光定量pcr、细胞转染、原位杂交（ISH）和激光共聚焦显微镜。在这里，我们发现TXL剂量依赖性地降低了组织、血清和细胞中miR-21的表达。过表达miR-21可通过上调smad3/p-smad3表达和下调smad7表达，提高α-平滑肌肌动蛋白（SMA）表达，降低E-cadherin表达。有趣的是，TXL还通过调节miR-21的表达，增加E-cadherin的表达，降低α-SMA的表达。更重要的是，TXL降低了IV型胶原蛋白、纤维连接蛋白、肾小球基底膜、肾小球面积和白蛋白/肌酐比值，提高了肌酐清除率。结果表明，TXL通过调节miR-21诱导的EMT改善肾脏结构和功能，这是保护DN的机制之一，miR-21可能是TXL在DN中的治疗靶点之一。
Diabetic nephropathy (DN) is one of the most important diabetic microangiopathies. The epithelial-to-mesenchymal transition (EMT) plays an important role in DN. The physiological role of microRNA-21 (miR-21) was closely linked to EMT. However, it remained elusive whether tongxinluo (TXL) ameliorated renal structure and function by regulating miR-21-induced EMT in DN. This study aimed to determine the effect of TXL on miR-21-induced renal tubular EMT and to explore the relationship between miR-21 and TGF-β1/smads signals. Real-time RT-PCR, cell transfection, in situ hybridization (ISH), and laser confocal microscopy were used, respectively. Here, we revealed that TXL dose dependently lowered miR-21 expression in tissue, serum, and cells. Overexpression of miR-21 can enhance α-smooth muscle actin (SMA) expression and decrease E-cadherin expression by upregulating smad3/p-smad3 expression and downregulating smad7 expression. Interestingly, TXL also increased E-cadherin expression and decreased α-SMA expression by regulating miR-21 expression. More importantly, TXL decreased collagen IV, fibronectin, glomerular basement membrane, glomerular area, and the albumin/creatinine ratio, whereas it increased the creatinine clearance ratio. The results demonstrated that TXL ameliorated renal structure and function by regulating miR-21-induced EMT, which was one of the mechanisms to protect against DN, and that miR-21 may be one of the therapeutic targets for TXL in DN.