The effect of SOX9 on islet β cells in high glucose environment through regulation of ERK/P38 signaling pathway.

Abstract

Islet beta cells are involved in insulin secretion. SRY-related high mobility group 9 (SX-S9) is involved in the progression of various diseases, but the role of SOX9 in islet β cells remains unclear. The islet β cell MIN6 cells were cultured in vitro and randomly divided into control group, high glucose group, and SOX9 siRNA group followed by analysis of SOX9 mRNA and protein expression by real-time PCR and Western blot, respectively, cell proliferation by MTT assay, cell apoptosis by flow cytometry, secretion of inflammatory factors TNF-α and IL-2 by ELISA, insulin secretion levels by spectrophotometer, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities, as well as ERK/P38 signaling protein expression by Western blot. Under high glucose environment, SOX9 mRNA and protein expression were significantly increased, MIN6 cell proliferation was inhibited, apoptosis rate and secretion of TNF-α and IL-2 were increased, along with decreased insulin secretion, increased MPO content, decreased SOD activity and phosphorylation of ERK/P38, compared with control group (p < 0.05). However, transfection of SOX9 siRNA reduced SOX9 expression, promoted proliferation of MIN6 cells, decreased apoptotic rate and secretion of TNF-α and IL-2, increased insulin secretion, decreased MPO content, increased SOD and ERK/P38 protein phosphorylation. Compared with high glucose group, the differences were statistically significant (p < 0.05). The expression of SOX9 is increased under high glucose environment. Down-regulation of SOX9 expression can inhibit islet cell apoptosis, oxidative stress and inflammation, and promote islet cell proliferation and insulin secretion by regulating ERK/P38 signaling pathway.