title: Nectin-like molecule-5 regulates intimal thickening after carotid artery ligation in mice.
abstract: OBJECTIVE
  Intimal thickening is considered to result from the dedifferentiation of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype, and their subsequent migration and proliferation. It is unknown whether nectin-like molecule (Necl)-5, which is overexpressed in cancer cells, is involved in intimal thickening.
  
  
  RESULTS
  Necl-5 was upregulated in mouse carotid artery after ligation. Compared with wild-type mice, intimal thickening after carotid artery ligation was milder in Necl-5 knockout mice. In vitro, the expression levels of SMC differentiation markers were higher, whereas the expression level of an SMC dedifferentiation marker was lower, in Necl-5 knockout mouse aortic SMCs (MASMCs) compared with wild-type MASMCs. The migration, proliferation, and extracellular signal-regulated kinase activity in response to serum were decreased in Necl-5 knockout MASMCs compared with wild-type MASMCs. In wild-type MASMCs, inhibition of extracellular signal-regulated kinase activity increased the expression levels of SMC differentiation markers and decreased their migration and proliferation in response to serum.
  
  
  CONCLUSIONS
  The present findings indicate that Necl-5 plays a role in the formation of intimal thickening after carotid artery ligation by regulating dedifferentiation, migration, and proliferation of SMCs in an extracellular signal-regulated kinase-dependent manner. Our results suggest that Necl-5 may represent a potential therapeutic target to limit intimal thickening after vascular injury.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Kureha
authors.forename: Seimi
authors.initials: S
authors.lastname: Satomi-Kobayashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kubo
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kinugasa
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
mesh_terms: D000818:Animals; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008026:Ligation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D000075983:Nectins; D011897:Random Allocation; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D000075983:Nectins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: atherosclerosis; cell adhesion molecules; differentiation; intimal thickening; smooth muscle cells