MicroRNA‐146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury

• Published in: Stem cells translational medicine 2016-10, Vol.5 (10), p.1406-1415
• Main Authors: Zhu, Yuan, Yu, Jing, Yin, Lei, Zhou, Ying, Sun, Zixuan, Jia, Haoyuan, Tao, Yang, Liu, Wanzhu, Zhang, Bin, Zhang, Jiao, Wang, Mei, Zhang, Xu, Yan, Yongmin, Xue, Jianguo, Gu, Hongbin, Mao, Fei, Xu, Wenrong, Qian, Hui
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - pathology; Administrative support; Animals; Apoptosis; Biomarkers; Blotting, Western; Bone marrow; Cell proliferation; Cell survival; Cisplatin; Cisplatin - toxicity; Cross-Linking Reagents - toxicity; Data analysis; Epithelial cells; ErbB-2 protein; Gene expression; Gene Expression Regulation; Grants; Growth factors; Higher education; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Ischemia; Kidneys; Liver cancer; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchyme; MicroRNA-146b; MicroRNAs; MicroRNAs - metabolism; miRNA; Oligonucleotide Array Sequence Analysis; Penicillin; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptor, ErbB-4 - biosynthesis; Stem cell transplantation; Thyroid cancer; Tissue Array Analysis; Tissue Engineering and Regenerative Medicine
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2015-0355

Altered microRNAs in renal tissues from cisplatin‐induced acute kidney injury (AKI) rats treated with or without rat bone marrow mesenchymal stem cells were profiled. MicroRNA‐146b (miR‐146b) inhibition induced ErbB4 expression, resulting in enhanced proliferation of injured renal tubular epithelial cells. Elevated miR‐146b expression contributed 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. 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. Significance The present study found that microRNA‐146b (miR‐146b) might be a novel biomarker for acute kidney injury and an indicator for its recovery after treatment with mesenchymal stem cells (MSCs). The results showed that in acute kidney injury induced by cisplatin, miR‐146b in serum increased more quickly than did the usual indexes of kidney injury and decreased with restoration of MSCs. In addition, inhibition of m