Glis2 inhibits the epithelial-mesenchymal transition and apoptosis of renal tubule cells by regulating the β-catenin signalling pathway in diabetic kidney disease.

Increasing evidence has supported the idea that epithelial-to-mesenchymal transition (EMT)-based tubulointerstitial fibrosis and the apoptosis of renal tubular epithelial cells (TECs) play important roles in the occurrence and development of Diabetic kidney disease (DKD). Glis2 is abundantly expressed in renal tubules and is a member of the Kruppel-like zinc finger transcription factor family, which is involved in the regulation of normal renal development and function. Glis2 deficiency may be closely associated with tubular atrophy and fibrosis, but the role played by Glis2 in DKD remains unclear. In this study, we found that Glis2 protein expression was downregulated in kidney tissue samples obtained by biopsy from DKD patients as well as HK-2 cells cultured in high-glucose medium, and overexpression of the Glis2 plasmid inhibited the apoptosis and EMT of TECS under HG conditions. In addition, Glis2 overexpression obliterated the activation of the β-catenin signalling pathway in HG-cultured HK-2 cells. Moreover, the β-catenin inhibitor XAV939 or XAV939 combined with Glis2 overexpression markedly inhibited the apoptosis and EMT of HG-treated HK-2 cells. All these findings indicated that upregulation of Glis2 expression might attenuate the EMT and apoptosis of renal tubule cells via the β-catenin signalling pathway under HG conditions. This outcome may lead to a better understanding of the pathogenesis of DKD and provide new insights into prevention and treatment strategies targeting DKD.