Hic-5, an adaptor protein expressed in vascular smooth muscle cells, modulates the arterial response to injury in vivo.
Focal adhesion components are targets for biochemical and mechanical stimuli that evoke crucial injury. Hic-5 (hydrogen peroxide-inducible clone 5) is a multidomain adaptor protein which is implicated in the regulation of integrin signaling in focal adhesion. The aim of this research was to test the hypothesis that Hic-5, a focal adhesion LIM protein expressed in smooth muscle cells, is involved in dynamic processes by pathological stimuli in the vessel wall. Here, we describe the analysis of the function of Hic-5 using a mouse model of vascular injury that may mimic balloon angioplasty. At 4 days after vascular injury, marked down-regulation of the Hic-5 expression was observed in the smooth muscle layer, and local delivery of the Hic-5 using adenovirus vectors repressed injury-induced neointimal expansion. In addition, Hic-5 reduced cells migration into three-dimensional collagen gels, and the forced expression of Hic-5 in cells embedded in the collagen gel matrix repressed the expression of uPA that participates in smooth muscle cell migration. These results suggest that Hic-5 modulates cellular responses to pathological stimuli in the vessel wall.
Kim-Kaneyama
Joo-ri
JR
Department of Microbiology, Showa University School of Pharmaceutical Sciences, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. shuri@pharm.showa-u.ac.jp
Wachi
Nanae
N
Sata
Masataka
M
Enomoto
Soichiro
S
Fukabori
Kiyoko
K
Koh
Keitatsu
K
Shibanuma
Motoko
M
Nose
Kiyoshi
K
D000256:Adenoviridae; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D022001:Focal Adhesions; D005782:Gels / Q000737:chemistry; D006801:Humans; D006965:Hyperplasia; D060588:LIM Domain Proteins; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D014161:Transduction, Genetic; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005782:Gels; D060588:LIM Domain Proteins; C090090:Tgfb1i1 protein, mouse; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator