Novel small leucine-rich repeat protein podocan is a negative regulator of migration and proliferation of smooth muscle cells, modulates neointima formation, and is expressed in human atheroma.
Circulation
; 128(22): 2351-63, 2013 Nov 26.
Article
en En
| MEDLINE
| ID: mdl-24043300
ABSTRACT
BACKGROUND:
Smooth muscle cell (SMC) migration and proliferation critically influence the clinical course of vascular disease. We tested the effect of the novel small leucine-rich repeat protein podocan on SMC migration and proliferation using a podocan-deficient mouse in combination with a model of arterial injury and aortic explant SMC culture. In addition, we examined the effect of overexpression of the human form of podocan on human SMCs and tested for podocan expression in human atherosclerosis. In all these conditions, we concomitantly evaluated the Wnt-TCF (T-cell factor) pathway. METHODS ANDRESULTS:
Podocan was strongly and selectively expressed in arteries of wild-type mice after injury. Podocan-deficient mice showed increased arterial lesion formation compared with wild-type littermates in response to injury (P<0.05). Also, SMC proliferation was increased in arteries of podocan-deficient mice compared with wild-type (P<0.05). In vitro, migration and proliferation were increased in podocan-deficient SMCs and were normalized by transfection with the wild-type podocan gene (P<0.05). In addition, upregulation of the Wnt-TCF pathway was found in SMCs of podocan-deficient mice both in vitro and in vivo. On the other hand, podocan overexpression in human SMCs significantly reduced SMC migration and proliferation, inhibiting the Wnt-TCF pathway. Podocan and a Wnt-TCF pathway marker were differently expressed in human coronary restenotic versus primary lesions.CONCLUSIONS:
Podocan appears to be a potent negative regulator of the migration and proliferation of both murine and human SMCs. The lack of podocan results in excessive arterial repair and prolonged SMC proliferation, which likely is mediated by the Wnt-TCF pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteínas
/
Movimiento Celular
/
Placa Aterosclerótica
/
Neointima
/
Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Circulation
Año:
2013
Tipo del documento:
Article