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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Vitamin D protects glomerular mesangial cells from high glucose-induced injury by repressing JAK/STAT signaling

Yiya Yang1, Yuting Lei1, Yumei Liang1

  • 1Department 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.

International Urology and Nephrology
|May 4, 2021
PubMed
Abstract

Insights

Vitamin D (VD) protects kidney cells from high glucose damage by inhibiting the JAK/STAT pathway. This suggests VD is a potential treatment for diabetic nephropathy by reducing fibronectin production.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • High glucose (HG) triggers TGF-β and ROS production, activating JAK/STAT signaling.
  • This pathway promotes matrix protein synthesis, contributing to diabetic nephropathy (DN) pathogenesis.
  • Investigating protective agents against HG-induced kidney injury is crucial.

Purpose of the Study:

  • To investigate the protective role of vitamin D (VD) in kidney cells under high glucose conditions.
  • To elucidate the molecular mechanisms underlying VD's potential renoprotective effects.

Main Methods:

  • Rat glomerular mesangial cells were cultured in high glucose medium.
  • Cells were treated with VD or vitamin D receptor (VDR) siRNAs.
  • TGF-β, fibronectin, JAK/STAT pathway components, and downstream gene expression were analyzed using qRT-PCR, immunoblotting, and ELISA.

Main Results:

  • VD treatment suppressed tyrosine phosphorylation of JAK2, STAT1, and STAT3.
  • VD inhibited TGF-β and fibronectin expression, effects reversed by VDR siRNA and a STATs inhibitor.
  • VD repressed JAK/STAT downstream genes (SOCS1, SOCS3, type IV collagen) and modulated specific microRNAs (miR-181a/b downregulated, miR-34a/Let-7b upregulated).

Conclusions:

  • Vitamin D inhibits high glucose-induced fibronectin production via the JAK/STAT pathway.
  • VD demonstrates renoprotective effects by repressing JAK/STAT signaling in glomerular mesangial cells.
  • These findings support VD's potential as a therapeutic strategy for diabetic nephropathy.
Keywords:
Glumerular cellHigh glucoseJAK/STATReactive oxygen speciesVitamin D

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