Exp Mol Med.
2006 Apr;38(2):153-161.
betaig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through alphavbeta5 integrin
- Affiliations
-
- 1Department of Biochemistry and Cell and Matrix Biology Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea. iskim@mail.knu.ac.kr
- 2Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
- 3Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Abstract
- Adhesion and migration of vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of atherosclerosis. These processes involve the interaction of VSMCs with extracellular matrix proteins. Here, we investigated integrin isoforms and signaling pathways mediating the adhesion and migration of VSMCs on betaig-h3, a transforming growth factor (TGF)-beta-inducible extracellular matrix protein that is elevated in atherosclerotic plaques. Adhesion assays showed that the alphavbeta5 integrin is a functional receptor for the adhesion of aortic VSMCs to betaig-h3. An YH18 motif containing amino acids between 563 and 580 of betaig-h3 was an essential motif for the adhesion and growth of VSMCs. Interaction between the YH18 motif and the alphavbeta5 integrin was responsible for the migration of VSMCs on betaig-h3. Inhibitors of phosphatidylinositide 3-kinase, extracellular signal-regulated kinase (ERK), and Src kinase reduced the adhesion and migration of VSMCs on betaig-h3. betaig-h3 triggered phosphorylation and activation of AKT, ERK, focal adhesion kinase, and paxillin mediating the adhesion and migration of VSMCs. Taken together, these results suggest that betaig-h3 and alphavbeta5 integrin play a role in the adhesion and migration of VSMCs during the pathogenesis of atherosclerosis.
Keyword
MeSH Terms
-
src-Family Kinases/antagonists & inhibitors
Transforming Growth Factor beta/genetics/*physiology
Signal Transduction/*physiology
Receptors, Vitronectin/genetics/*physiology
Protein-Tyrosine Kinases/antagonists & inhibitors
Paxillin/metabolism
Myocytes, Smooth Muscle/drug effects/metabolism
Muscle, Smooth, Vascular/cytology/drug effects/*metabolism
Morpholines/pharmacology
Molecular Sequence Data
Integrins/genetics/*physiology
Humans
Flavonoids/pharmacology
Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors
Extracellular Matrix Proteins/genetics/*physiology
Enzyme Inhibitors/pharmacology
Chromones/pharmacology
Cells, Cultured
Cell Movement/*physiology
Cell Adhesion/physiology
Animals
Amino Acid Sequence
Amino Acid Motifs/genetics
1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Integrins Mediating Adhesion and Proliferation of ADP-stimulated Vascular Smooth Muscle Cells
- Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with alpha3beta1 integrin
- Effect of Transforming Growth Factor-Induced Gene Product, beta ig-h3 on Proliferation, Migration, and Adhesion of Aortic Smooth Muscle Cells Cultured in High Glucose
- Effect and Mechanism of High Glucose Level on the Expression of an Adhesion Protein, beta ig-h3, and Cellular Function in Endothelial Cells
- Statins Inhibited the ADP-Stimulated Activation of Integrins alpha v beta5 and alpha v beta3 of Vascular Smooth Muscle Cells
