Involvement of betaPIX in angiotensin II-induced migration of vascular smooth muscle cells.
10.3858/emm.2009.41.6.044
- Author:
Eun Young SHIN
1
;
Chan Soo LEE
;
Mee Hee PARK
;
Duk Joong KIM
;
Sahng June KWAK
;
Eung Gook KIM
Author Information
1. Department of Biochemistry and Signaling Disorder Research Center, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea. egkim@chungbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
angiotensin II;
cell movement;
cytoskeleton;
muscle, smooth, vascular;
rho guanine nucleotide exchange factors
- MeSH:
1-Phosphatidylinositol 3-Kinase/metabolism;
Angiotensin II/*metabolism;
Animals;
*Cell Movement;
Cells, Cultured;
Guanine Nucleotide Exchange Factors/genetics/*metabolism;
Muscle, Smooth, Vascular/cytology;
Myocytes, Smooth Muscle/*cytology;
NADPH Oxidase/metabolism;
Protein Kinase C/metabolism;
RNA, Small Interfering/genetics;
Rats;
Rats, Sprague-Dawley;
p21-Activated Kinases/metabolism;
rac1 GTP-Binding Protein/metabolism;
src-Family Kinases/metabolism
- From:Experimental & Molecular Medicine
2009;41(6):387-396
- CountryRepublic of Korea
- Language:English
-
Abstract:
Angiotensin II (Ang II) stimulates migration of vascular smooth muscle cell (VSMC) in addition to its contribution to contraction and hypertrophy. It is well established that Rho GTPases regulate cellular contractility and migration by reorganizing the actin cytoskeleton. Ang II activates Rac1 GTPase, but its upstream guanine nucleotide exchange factor (GEF) remains elusive. Here, we show that Ang II-induced VSMC migration occurs in a betaPIX GEF-dependent manner. betaPIX-specific siRNA treatment significantly inhibited Ang II-induced VSMC migration. Ang II activated the catalytic activity of betaPIX towards Rac1 in dose- and time-dependent manners. Activity reached a peak at 10 min and declined close to a basal level by 30 min following stimulation. Pharmacological inhibition with specific kinase inhibitors revealed the participation of protein kinase C, Src family kinase, and phosphatidylinositol 3-kinase (PI3-K) upstream of betaPIX. Both p21-activated kinase and reactive oxygen species played key roles in cytoskeletal reorganization downstream of betaPIX-Rac1. Taken together, our results suggest that betaPIX is involved in Ang II-induced VSMC migration.
