Abstract
Severe injury of renal tubular epithelial cells may cause acute renal failure, the progression of which results in renal fibrosis, and obstructive nephropathy. Transforming growth factor β 1 and bone morphogenic protein 7 (BMP7) play contradicting roles in and coordinate the process of epithelial-to-mesenchymal transition of renal tubular epithelial cells, but the molecular regulation of BMP7 remains ill-defined. Here, we addressed this question. We found that after induction of unilateral ureteral obstruction (UUO) in mice, the increases in BMP7 mRNA were much more pronounced than BMP7 protein in kidney, suggesting the presence of post-transcriptional control of BMP7. Moreover, significant increases in a BMP7-targeting microRNA, miR-384-5p, were detected in the mouse kidney post UUO. Overexpression of miR-384-5p significantly decreased BMP7 protein, while depletion of miR-384-5p significantly increased BMP7 protein in renal epithelial cells. Bioinformatics study showed that miR-384-5p appeared to suppress BMP7 protein translation, through its direct binding to the 3′-UTR of BMP7 mRNA. Furthermore, suppression of miR-384-5p in vivo attenuated severity of renal injury by UUO. Together, our study sheds light on miR-384-5p as a crucial factor that regulates the fibrosis-related pathogenesis after renal injury, and points to miR-384-5p as a promising innovative therapeutic target for prevention of renal fibrosis.
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The study was supported by the National Natural Foundation Self-support Program (No. 81200528).
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Sun, J., Yin, A., Zhao, F. et al. Protection of tubular epithelial cells during renal injury via post-transcriptional control of BMP7. Mol Cell Biochem 435, 141–148 (2017). https://doi.org/10.1007/s11010-017-3063-4
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DOI: https://doi.org/10.1007/s11010-017-3063-4