MicroRNA‐146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury
MicroRNA‐146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury
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DOI：
10.5966/sctm.2015-0355
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发表时间：
2016-07
影响因子：
6
通讯作者：
Yuan Zhu;Jing Yu;L. Yin;Ying Zhou;Zixuan Sun;H. Jia;Yang Tao;Wanzhu Liu;Bin Zhang
中科院分区：
文献类型：
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作者：
Yuan Zhu;Jing Yu;L. Yin;Ying Zhou;Zixuan Sun;H. Jia;Yang Tao;Wanzhu Liu;Bin Zhang
间充质干细胞（MSCs）在肾损伤修复中的作用已被广泛研究。然而，潜在的分子机制尚不清楚。我们分析了顺铂诱导的急性肾损伤（AKI）大鼠在接受或不接受大鼠骨髓间充质干细胞（rMSCs）治疗后肾组织中microrna的变化。我们观察到，与健康大鼠相比，AKI大鼠肾组织中的microRNA - 146b （miR - 146b）表达显著上调，顺铂给药后MSC治疗后表达降低。在AKI早期，血清miR - 146b水平迅速升高，甚至快于两项常规肾功能指标：血清肌酐和血尿素氮水平。此外，AKI患者的血清miR - 146b水平高于健康人群。体外暴露于顺铂也增加miR - 146b在肾小管上皮细胞（TECs）中的表达。miR - 146b敲低可保护顺铂诱导的肾tec细胞凋亡，并促进其增殖。此外，ErbB4被确定为miR‐146b的直接靶点，miR‐146b抑制诱导ErbB4表达，导致受损肾tec的增殖增强。此外，rMSCs的修复可以通过下调ErbB4来控制。总之，miR - 146b表达升高有助于顺铂诱导的AKI，部分原因是ErbB4下调。miR - 146b可能是AKI的早期生物标志物，miR - 146b抑制可能是AKI治疗的新策略。
The role of mesenchymal stem cells (MSCs) in kidney injury repair has been studied widely. However, the underlying molecular mechanism remains unclear. We profiled the altered microRNAs in renal tissues from cisplatin‐induced acute kidney injury (AKI) rats treated with or without rat bone marrow MSCs (rMSCs). We observed that microRNA‐146b (miR‐146b) expression was considerably upregulated in renal tissues from AKI rats compared with that in healthy rats, and the expression decreased following MSC treatment after cisplatin administration. At the early stage of AKI, serum miR‐146b levels exhibited a rapid increase that was even faster than that of two conventional renal function indexes: serum creatinine and blood urea nitrogen levels. Furthermore, the serum miR‐146b levels in AKI patients were higher than those in healthy people. In vitro exposure to cisplatin also increased miR‐146b expression in renal tubular epithelial cells (TECs). miR‐146b knockdown protected renal TECs from cisplatin‐induced apoptosis and promoted their proliferation. Moreover, ErbB4 was identified as a direct target of miR‐146b, and miR‐146b inhibition induced ErbB4 expression, resulting in enhanced proliferation of injured renal TECs. In addition, restoration by rMSCs could be controlled through ErbB4 downregulation. In conclusion, elevated miR‐146b expression contributes to cisplatin‐induced AKI, partly through ErbB4 downregulation. miR‐146b might be an early biomarker for AKI, and miR‐146b inhibition could be a novel strategy for AKI treatment.