miR-199b-5p mediates adriamycin-induced podocyte apoptosis by inhibiting the expression of RGS10

Exp Ther Med. 2021 Dec;22(6):1469. doi: 10.3892/etm.2021.10904. Epub 2021 Oct 21.

Abstract

Podocyte apoptosis is a key risk factor for the progression of kidney diseases. MicroRNA (miR)-199b-5p has been shown to be involved in cell apoptosis. However, the molecular mechanisms of miR-199b-5p in podocyte apoptosis remain uncertain. Thus, the present study aimed to investigate whether miR-199b-5p participates in the regulation of podocyte apoptosis and to elucidate the involved mechanisms of this process. A podocyte apoptosis model was constructed using adriamycin (ADR) in vitro. miR-199b-5p mimic and inhibitor were transfected in podocytes to change the expression level of miR-199b-5p. RNA expression was examined by reverse transcription-quantitative PCR. Western blotting was used to measure protein expression. Apoptosis was monitored via flow cytometry and detection of apoptosis-associated proteins. The results from the present study demonstrated that miR-199b-5p was upregulated and that regulator of G-protein signaling 10 (RGS10) was downregulated in ADR-stimulated podocytes. Overexpression of miR-199b-5p could inhibit RGS10 expression and stimulate podocyte apoptosis, whereas miR-199b-5p knockdown restored the levels of RGS10 and ameliorated podocyte apoptosis in ADR-induced podocytes. Furthermore, the effects of miR-199b-5p overexpression could be significantly reversed by RGS10 overexpression. In addition, podocyte transfection of miR-199b-5p activated the AKT/mechanistic target of rapamycin (mTOR) signaling, which was blocked following RGS10 overexpression. Taken together, the present study demonstrated that miR-199b-5p upregulation could promote podocyte apoptosis by inhibiting the expression of RGS10 through the activation of AKT/mTOR signaling.

Keywords: AKT/mechanistic target of rapamycin signaling pathway; apoptosis; microRNA-199b-5p; podocyte; regulator of G-protein signaling 10.

Grants and funding

Funding: This study was supported by the National Natural Science Foundation of China (grant no. 81970664), the Natural Science Foundation of Jiangsu Province (grant no. BK20191083), the 789 Outstanding Talent Program of SAHNMU (grant nos. 789ZYRC202080119 and 789ZYRC202090251) and the Science and Technology Development Foundation of Nanjing Medical University (grant no. NMUB2020052).