MicroRNA21/HDAC4 mediates podocyte apoptosis under high glucose conditions by regulating the activation of FoxO1

This is the authors' abstract. We don't add key points for this paper.

Diabetic kidney disease (DKD), which lacks effective treatment, has become the leading cause of end-stage renal disease. Apoptosis of podocytes, as a vital mode of cell injury, plays an important role in the progression of DKD. MicroRNA-21 (miR-21) and Forkhead transcription Factor O1 (FoxO1) have been revealed to act in DKD, but the mechanisms remain elusive. Here, we investigated the special regulatory mechanism by which miR-21 activates FoxO1 in mouse podocytes induced by high glucose (HG). In vitro, after exposure to HG, podocyte apoptosis, miR-21, HDAC4, FoxO1/acetylate-FoxO1/phosphorylate-FoxO1, Bcl-2, and nephrin were examined. Then, we evaluated the vital effect of miR-21 in regulating podocyte apoptosis and identified the critical activator of FoxO1 by overexpression or inhibition of miR-21/HDAC4 via adenoviral transfer. The results showed that HG increased podocyte apoptosis, elevated the expression of miR-21, HDAC4, acetylate-FoxO1, and FoxO1, and reduced the expression of Bcl-2 and nephrin. In addition, overexpression or inhibition of miR-21 could affect the levels of HDAC4, acetylated FoxO1, FoxO1, Bcl-2, and nephrin. Finally, overexpression of HDAC4 decreased the acetylation of FoxO1 while increasing the phosphorylation of FoxO1, which resulted in a decline in Bcl-2 and nephrin. Therefore, these data indicated that miR-21/FoxO1 was a key pathway in regulating podocyte apoptosis under HG conditions. Furthermore, phosphorylation rather than acetylation was the critical activator of FoxO1.