Human umbilical cord-derived mesenchymal stem cells enhanced HK-2 cell autophagy through MicroRNA-145 by inhibiting the PI3K/AKT/mTOR signaling pathway

Abstract

Recent studies have shown that autophagy exhibits a protective role in acute kidney injury (AKI), and the accumulation of advanced oxidation protein products (AOPP) participates in the progression of kidney diseases. Our previous study indicated that AOPP induced injury in renal tubular epithelial cells (RTECs) through autophagy inhibition. Besides, we found that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) enhanced autophagy in AOPP-treated RTECs, but the underlying mechanism remains unclear. We regulated microRNA-145 (miR-145) expression in HK-2 cells (a cell line of RTECs), or co-cultured hUC-MSCs with HK-2 cells and studied the autophagic activity in HK-2 cells to explore the underlying mechanism. Our data demonstrated that upregulated miR-145 increased LC3 II and Beclin 1 levels, decreased p62 level, three autophagy related proteins, inhibited the phosphorylation of PI3K/AKT/mTOR, and increased LC3B-positive staining and the autophagosome number. Furthermore, hUC-MSCs enhanced autophagy and inhibited phosphorylation of PI3K/AKT/mTOR in AOPP-treated HK-2 cells, which was then partially rescued using miR-145 knockdown in the hUC-MSCs co-culture system. In conclusion, our study showed that hUC-MSCs enhanced autophagy in AOPP-treated HK-2 cells mediated by miR-145 via inhibition of the PI3K/AKT/mTOR pathway, which indicated that hUC-MSCs might serve as a prospective therapy for AKI.