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.

Published

Journal Article

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 AND RESULTS: 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.

Full Text

Duke Authors

Cited Authors

  • Hutter, R; Huang, L; Speidl, WS; Giannarelli, C; Trubin, P; Bauriedel, G; Klotman, ME; Fuster, V; Badimon, JJ; Klotman, PE

Published Date

  • November 26, 2013

Published In

Volume / Issue

  • 128 / 22

Start / End Page

  • 2351 - 2363

PubMed ID

  • 24043300

Pubmed Central ID

  • 24043300

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.113.004634

Language

  • eng

Conference Location

  • United States