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HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box.

Authors: Doi, H  Iso, T  Yamazaki, M  Akiyama, H  Kanai, H  Sato, H  Kawai-Kowase, K  Tanaka, T  Maeno, T  Okamoto, E  Arai, M  Kedes, L  Kurabayashi, M 
Citation: Doi H, etal., Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2328-34. Epub 2005 Sep 8.
Pubmed: (View Article at PubMed) PMID:16151017
DOI: Full-text: DOI:10.1161/01.ATV.0000185829.47163.32

OBJECTIVE: Myocardin is a coactivator of serum response factor (SRF) required for vascular smooth muscle cell (VSMC) differentiation. HERP1 is a transcriptional repressor, which is abundantly expressed in vascular system and is known to function as a target gene of Notch. However, the role of HERP1 in the pathogenesis of vascular lesions remains unknown. The present study characterizes the expression of HERP1 in normal and diseased vessels, and tests the hypothesis that HERP1 inhibits SRF/myocardin-dependent SMC gene expression. METHODS AND RESULTS: Immunohistochemistry revealed that HERP1 and myocardin expression was localized to SMC in the neointima of balloon-injured rat aorta and in human coronary atherosclerotic lesions. Expression of both HERP1 and myocardin was elevated in cultured VSMCs compared with medial SMC. Overexpressed HERP1 inhibited the myocardin-induced SMC marker gene expression in 10T1/2 cells. HERP1 protein interfered with the SRF/CArG-box interaction in vivo and in vitro. Immunoprecipitation assays showed that HERP1 physically interacts with SRF. CONCLUSIONS: HERP1 expression was associated with the SMC proliferation and dedifferentiation in vitro and in vivo. HERP1 may play a role in promoting the phenotypic modulation of VSMCs during vascular injury and atherosclerotic process by interfering with SRF binding to CArG-box through physical association between HERP1 and SRF.

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CRRD Object Information
CRRD ID: 8554320
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.