title: Effects of caveolin-1 and P-ERK1/2 on Ang II-induced glomerular mesangial cell proliferation.
abstract: This study explored the effects of caveolin-1, p-ERK1/2 and transient receptor potential channel 6 (TRPC6) on angiotensin II (Ang II)-induced glomerular mesangial cell (GMC) proliferation, and investigated the role of Ang II on GMC proliferation. GMC cultures were divided into Control, Ang II (Ang II 10(-7 )mol/L), PD98059 (Ang II 10(-7 )mol/L + PD98059 5 × 10(-5 )mol/L) and MβCD groups (Ang II 10(-7 )mol/L + MβCD 10(-2 )mol/L). GMCs proliferation was measured by the methyl thiazolil tetracolium and trypan blue assays. The distribution of caveolin-1, p-ERK1/2 and TRPC6 was monitored by immunocytochemistry. Real time polymerase chain reaction (PCR) was used to assess mRNA expression of caveolin-1 and TRPC6. Western blot analysis was used to assess protein expression of caveolin-1, p-ERK1/2 and TRPC6. The results showed that Ang II promoted GMC proliferation. PD98059 and MβCD blocked Ang II-induced GMC proliferation, by 31.06% and 48.96%, respectively. In comparison with the control group, the expression of p-ERK1/2 and TRPC6 was significantly higher and caveolin-1 expression was significantly lower in the Ang II group. PD98059 markedly decreased p-ERK1/2 and TRPC6 expression and increased caveolin-1 expression. MβCD decreased the expression of p-ERK1/2 and TRPC6, but had no significant effect on caveolin-1 protein expression. These findings suggested that the intact caveolae structure was associated with Ang II-induced GMC proliferation, ERK1/2 activation and TRPC6 expression. And p-ERK1/2 acted as an upstream signal molecule for TRPC6. Moreover, p-ERK1/2 and caveolin-1 appeared to be inhibited reciprocally, thus regulated GMC proliferation by regulating TRPC6 expression.
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Guangzhou Medical University, No. 195 Dongfeng Xi Road, Guangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Zequan
authors.initials: Z
authors.lastname: Ji
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D050527:Mesangial Cells / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases