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KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells.

Authors: Zhao, LM  Su, XL  Wang, Y  Li, GR  Deng, XL 
Citation: Zhao LM, etal., Lab Invest. 2013 Feb;93(2):159-67. doi: 10.1038/labinvest.2012.163. Epub 2012 Nov 19.
Pubmed: (View Article at PubMed) PMID:23212096
DOI: Full-text: DOI:10.1038/labinvest.2012.163

The mechanisms underlying the involvement of advanced glycation endproducts (AGEs) in diabetic atherosclerosis are not fully understood. The present study was designed to investigate whether intermediate-conductance Ca(2+)-activated K(+) channels (K(Ca)3.1 channels) are involved in migration and proliferation induced by AGEs in cultured rat vascular smooth muscle cells (VSMCs) using approaches of whole-cell patch voltage-clamp, cell proliferation and migration assay, and western blot analysis. It was found that the current density and protein level of K(Ca)3.1 channels were enhanced in cells incubated with AGE-BSA (bovine serum albumin), and the effects were reversed by co-incubation of AGE-BSA with anti-RAGE (anti-receptors of AGEs) antibody. The ERK1/2 inhibitors PD98059 and U0126, the P38-MAPK inhibitors SB203580 and SB202190, or the PI3K inhibitors LY294002 and wortmannin countered the K(Ca)3.1 channel expression by AGE-BSA. In addition, AGE-BAS increased cell migration and proliferation, and the effects were fully reversed with anti-RAGE antibody, the K(Ca)3.1 channel blocker TRAM-34, or K(Ca)3.1 small interfering RNA. These results demonstrate for the first time that AGEs-induced increase of migration and proliferation is related to the upregulation of K(Ca)3.1 channels in rat VMSCs, and the intracellular signals ERK1/2, P38-MAPK and PI3K are involved in the regulation of K(Ca)3.1 channel expression.

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RGD Object Information
RGD ID: 7244285
Created: 2013-05-31
Species: All species
Last Modified: 2013-05-31
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.