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

Abstract

: 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 miR-146b could ameliorate the apoptosis induced by cisplatin and potentially improve the proliferation by freeing ErbB4 and its downstream proteins.

• Authors: Yuan Zhu, Jing Yu, Lei Yin, Ying Zhou, Zixuan Sun, Haoyuan Jia, Yang Tao, Wanzhu Liu, Bin Zhang, Jiao Zhang, Mei Wang, Xu Zhang, Yongmin Yan, Jianguo Xue, Hongbin Gu, Fei Mao, Wenrong Xu, Hui Qian
• Journal: Stem cells translational medicine (Stem Cells Transl Med) Vol. 5 Issue 10 Pg. 1406-1415 (10 2016) ISSN: 2157-6564 [Print] England
• PMID: 27400799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©AlphaMed Press.

Chemical References

• Biomarkers
• Cross-Linking Reagents
• MIRN146 microRNA, human
• MicroRNAs
• Receptor, ErbB-4
• Cisplatin

Topics

• Acute Kidney Injury (pathology)
• Animals
• Biomarkers
• Blotting, Western
• Cisplatin (toxicity)
• Cross-Linking Reagents (toxicity)
• Gene Expression Regulation
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Mesenchymal Stem Cell Transplantation
• MicroRNAs (metabolism)
• Oligonucleotide Array Sequence Analysis
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Receptor, ErbB-4 (biosynthesis)
• Tissue Array Analysis