Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Podocyte damage is vital for the etiopathogenesis of diabetic nephropathy (DN). Klotho (KL), a multifunctional protein, has been demonstrated to have renoprotective effects; nevertheless, the mechanism for protective effect has not been completely elucidated. Transient receptor potential cation channel subfamily C, member 6 (TRPC6), a potential target of KL, is implicated in glomerular pathophysiology. Here, we sought to determine whether KL could protect against podocyte injury through inhibiting TRPC6 in DN. We found that high glucose (HG) triggered podocyte injury as manifested by actin cytoskeleton damage along with the downregulation of KL and Synaptopodin and the upregulation of TRPC6. KL overexpression reversed HG-induced podocytes injury, whereas cotreatment with TRPC6 activator flufenamic acid (FFA) significantly abrogated the beneficial effects conferred by KL. Moreover, KL knockdown in podocytes resulted in actin cytoskeleton impairment, decreased Synaptopodin expression, and increased TRPC6 expression. In db/db mice, KL overexpression inhibited TRPC6 expression and attenuated diabetes-induced podocyte injury, which was accompanied by decreased albuminuria and ameliorated glomerulosclerosis. Our data provided novel mechanistic insights for KL against DN and highlighted TRPC6 as a new target for KL in podocytes to prevent DN. Copyright © 2022 Xingmei Yao et al.

Citation

Xingmei Yao, Hengjiang Guo, Mengyao Sun, Sixuan Meng, Bingbing Zhu, Ji Fang, Jiebo Huang, Hao Wang, Lina Xing. Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy. Journal of diabetes research. 2022;2022:1329380

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 35480629

View Full Text