Yiya Yang1, Yuting Lei1, Yumei Liang1, Shuangshuang Fu1, Congjun Yang1, Kanghan Liu1, Yinyin Chen2. 1. Department of Nephrology and Laboratory of Kidney Disease, Changsha Clinical Research Center for Kidney DiseaseHunan Clinical Research Center for Chronic Kidney Disease, Hunan Provincial People's Hospital, Hunan Normal University, 61#, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China. 2. Department of Nephrology and Laboratory of Kidney Disease, Changsha Clinical Research Center for Kidney DiseaseHunan Clinical Research Center for Chronic Kidney Disease, Hunan Provincial People's Hospital, Hunan Normal University, 61#, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China. chenchenyinyin1212@163.com.
Abstract
AIM: High glucose (HG) induces the production of transforming growth factor (TGF)-β and reactive oxygen species, which further activates JAK/STAT signaling and promotes the synthesis of matrix proteins, contributes to the pathophysiological processes of diabetic nephropathy. This study aims to investigate the protection role of vitamin D (VD) in the kidney in high glucose condition. METHODS: Rat glomerular mesangial cells were cultured in high glucose medium, with or without VD or VD receptor (VDR) siRNAs treatment. The levels of TGF-β and fibronectin were detected by qRT-PCR, immunoblotting and enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated JAK2, STAT1 and STAT3, and JAK/STAT signaling downstream genes were examined by immunoblotting and qRT-PCR. RESULTS: In rat glomerular mesangial cells, VD treatment can repress the tyrosine phosphorylation of JAK2, STAT1 and STAT3. VD inhibited TGF-β and fibronectin expression which was rescued by vitamin d receptor (VDR) siRNA and STATs inhibitor perficitinib. The JAK/STAT signaling downstream protein coding genes including SOCS1, SOCS3 and type IV collagen were repressed by VD. Meanwhile, the expression of non-coding RNAs such as miR-181a, miR-181b, was repressed by VD, and the expression of miR-34a and Let-7b was upregulated by VD. CONCLUSION: Vitamin D (VD) treatment inhibits the function of HG on fibronectin production through regulating JAK/STAT pathway. These results provide direct evidences that VD protects glomerular mesangial cells from high glucose-induced injury through repressing JAK/STAT signaling, which has the potential for clinical DN treatment.
AIM: High glucose (HG) induces the production of transforming growth factor (TGF)-β and reactive oxygen species, which further activates JAK/STAT signaling and promotes the synthesis of matrix proteins, contributes to the pathophysiological processes of diabetic nephropathy. This study aims to investigate the protection role of vitamin D (VD) in the kidney in high glucose condition. METHODS:Rat glomerular mesangial cells were cultured in high glucose medium, with or without VD or VD receptor (VDR) siRNAs treatment. The levels of TGF-β and fibronectin were detected by qRT-PCR, immunoblotting and enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated JAK2, STAT1 and STAT3, and JAK/STAT signaling downstream genes were examined by immunoblotting and qRT-PCR. RESULTS: In rat glomerular mesangial cells, VD treatment can repress the tyrosine phosphorylation of JAK2, STAT1 and STAT3. VD inhibited TGF-β and fibronectin expression which was rescued by vitamin d receptor (VDR) siRNA and STATs inhibitor perficitinib. The JAK/STAT signaling downstream protein coding genes including SOCS1, SOCS3 and type IV collagen were repressed by VD. Meanwhile, the expression of non-coding RNAs such as miR-181a, miR-181b, was repressed by VD, and the expression of miR-34a and Let-7b was upregulated by VD. CONCLUSION:Vitamin D (VD) treatment inhibits the function of HG on fibronectin production through regulating JAK/STAT pathway. These results provide direct evidences that VD protects glomerular mesangial cells from high glucose-induced injury through repressing JAK/STAT signaling, which has the potential for clinical DN treatment.
Entities:
Keywords:
Glumerular cell; High glucose; JAK/STAT; Reactive oxygen species; Vitamin D
Authors: M A Gall; P Rossing; P Skøtt; P Damsbo; A Vaag; K Bech; A Dejgaard; M Lauritzen; E Lauritzen; P Hougaard Journal: Diabetologia Date: 1991-09 Impact factor: 10.122
Authors: Tarek Atia; Mohammad Zahidul Iqbal; Hassan Fathy Ahmed; Hader I Sakr; M H Abdelzaher; Deaa Fekri Morsi; Mostafa E Metawee Journal: J Evid Based Integr Med Date: 2022 Jan-Dec