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Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury
Christopher P. Regan, … , Cort S. Madsen, Gary K. Owens
Christopher P. Regan, … , Cort S. Madsen, Gary K. Owens
Published November 1, 2000
Citation Information: J Clin Invest. 2000;106(9):1139-1147. https://doi.org/10.1172/JCI10522.
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Article

Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury

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Abstract

While it is well established that phenotypic modulation of vascular smooth muscle cells (VSMCs) contributes to the development and progression of vascular lesions, little is known regarding the molecular mechanisms of phenotypic modulation in vivo. Here we show that vascular injury reduces transcription of VSMC differentiation marker genes, and we identify cis regulatory elements that may mediate this decrease. Using a carotid wire-injury model in mice carrying transgenes for smooth muscle α-actin, smooth muscle myosin heavy chain, or a SM22α promoter–β-gal reporter, we collected arteries 7 and 14 days after injury and assessed changes in endogenous protein and mRNA levels and in β-gal activity. Endogenous levels for all markers were decreased 7 days after injury and returned to nearly control levels by 14 days. β-gal staining in all lines followed a similar pattern, suggesting that transcriptional downregulation contributed to the injury-induced decreases. To begin to dissect this response, we mutated a putative G/C-rich repressor in the SM22α promoter transgene and found that this mutation significantly attenuated injury-induced downregulation. Hence, transcriptional downregulation contributes to injury-induced decreases in VSMC differentiation markers, an effect that may be partially mediated through a G/C-rich repressor element.

Authors

Christopher P. Regan, Paul J. Adam, Cort S. Madsen, Gary K. Owens

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Figure 1

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Western blot analysis of the SMMHC antibody used to assess changes in SM...
Western blot analysis of the SMMHC antibody used to assess changes in SMMHC protein levels after injury. Protein extracts from rat and mouse aorta, cultured VSMCs, and cultured endothelial cells were separated by SDS-PAGE, immobilized on a PVDF membrane and probed with a rabbit anti-chicken SMMHC antibody (17) as described in Methods. SM1 and/or SM2 isoforms of SMMHC were detected in protein extracts from mouse aorta (lane 1), rat aorta (lane 2), and cultured rat VSMCs (lane 3), but not cultured rat endothelial cells (lane 4).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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