RGD Reference Report - Integrin-linked kinase in the vascular smooth muscle cell response to injury. - Rat Genome Database

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Integrin-linked kinase in the vascular smooth muscle cell response to injury.

Authors: Ho, B  Hou, G  Pickering, JG  Hannigan, G  Langille, BL  Bendeck, MP 
Citation: Ho B, etal., Am J Pathol. 2008 Jul;173(1):278-88. Epub 2008 Jun 5.
RGD ID: 2301740
Pubmed: PMID:18535176   (View Abstract at PubMed)
PMCID: PMC2438304   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2008.071046   (Journal Full-text)

Integrin-mediated interactions between smooth muscle cells (SMCs) and the extracellular matrix regulate cell migration and proliferation during neointimal hyperplasia. Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffolding molecule that acts downstream of integrin receptors to modulate cell adhesion; therefore, we examined ILK function in SMCs during wound repair. Silencing of ILK expression with siRNA in vitro decreased cell adhesion to fibronectin and accelerated both cell proliferation and wound closure in the cell monolayer; it also resulted in the rearrangement of focal adhesions and diminished central actin stress fibers. Akt and GSK3beta are ILK substrates that are important in cell motility; however, ILK siRNA silencing did not attenuate injury-induced increases in Akt and GSK3beta phosphorylation. Following balloon catheter injury of the rat carotid artery in vivo, a dramatic decrease in ILK levels coincided with both the proliferation and migration of SMCs, which leads to the formation of a thickened neointima. Immunostaining revealed decreased ILK levels in the media and deep layers of the neointima, but increased ILK levels in the subluminal layers of the intima. Taken together, these results suggest that ILK functions to maintain SMC quiescence in the normal artery. A decrease in ILK levels after injury may permit SMC migration, proliferation, and neointimal thickening, and its re-expression at the luminal surface may attenuate this process during later stages of the injury response.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of smooth muscle cell migration  IMP 2301740reduction of wound healing in cultureRGD 
negative regulation of smooth muscle cell proliferation  IMP 2301740reduction of wound healing in cultureRGD 
positive regulation of cell-matrix adhesion  IMP 2301740 RGD 
protein phosphorylation  IDA 2301740 RGD 
supramolecular fiber organization  IMP 2301740fibronectin fibrils on SMCs in cultureRGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
focal adhesion  IDA 2301740 RGD 
stress fiber located_inIDA 2301740 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase activity  IDA 2301740 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ilk  (integrin-linked kinase)


Additional Information