Angiotensin II-transient receptor potential channel C6 signaling pathway mediates podocyte injury
10.3969/j.issn.2095-4344.2014.46.014
- VernacularTitle:足细胞损伤的诱导途径：血管紧张素Ⅱ-足细胞瞬时受体电位阳离子通道蛋白6信号通路
- Author:
Dandan YAO
;
Ruixia MA
;
Lihui ZHAI
;
Zuolin LI
;
Zhen LI
- Publication Type:Journal Article
- Keywords:
angiotensin II;
podocytes;
diabetes melitus;
TRPC cation channels
- From:
Chinese Journal of Tissue Engineering Research
2014;(46):7447-7451
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Transient receptor potential channel C6 (TRPC6) is a new and important slit diaphragm-associated protein in podocytes involved in regulating glomerular filter function. Glomerular TRPC6 expression is closely associated with proteinuria in diabetic kidney disease. OBJECTIVE: To investigate the expression of canonical TRPC6 in mouse podocytes induced by high glucose, and to explore the possible mechanism of diabetic kidney disease. METHODS:Mouse podocyte cels were cultured and divided into normal glucose group (5.6 mmol/L D-glucose), normal control group (5.6 mmol/L D-glucose+25 mmol/L mannitol) and experimental groups which were in the environment of high glucose (30 mmol/L). The experimental groups included high glucose group, valsartan treatment groups (10-5 mol/L) and U73122 control group (10μmol/L U73122). After 48 hours, the expressions of mRNA and proteins of TRPC6, nephrin and angiotensin II (AngII) were detected respectively by real-time quantitative PCR and western blot analysis. RESULTS AND CONCLUSION:Compared with the normal control group, the expressions of mRNA and proteins of TRPC6 and angiotensin II were markedly elevated in the high glucose group (P < 0.01), while the expressions of mRNA and proteins of nephrin were decreased (P < 0.01). The mRNA and proteins of TRPC6 and angiotensin II expressions were significantly down-regulated by valsartan (P < 0.05,P < 0.01), while the mRNA and protein expressions of nephrin were effectively up-regulated (P < 0.05). Compared with the high glucose group, the expressions of mRNA and proteins of TRPC6 and angiotensin II were ameliorated in the U73122 control group. The expressions of mRNA and proteins of TRPC6, nephrin and angiotensin II had no statistical significance between the normal control group and normal glucose group (P > 0.05). Angiotensin II-TRPC6 signaling pathway may mediate high glucose-induced podocyte injury, meanwhile it provides a new theoretical basis for the treatment of diabetic kidney disease, by which the angiotensin receptor blockers can protect podocytes in diabetic kidney disease.
