Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 317, Issue 3, Pages 801-810Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.03.115
Keywords
vascular smooth muscle; differentiation; transciption factors; Sp1/Sp3; proly hydroxylase; gene regulation; promoters; fibroblasts
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Funding
- NHLBI NIH HHS [T32 HL07824, R01 HL43302] Funding Source: Medline
- NIGMS NIH HHS [F31 GM15732] Funding Source: Medline
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SM-20 encodes all intracellular Prolyl hydroxylase that acts on hypoxia inducible factor (HIF)-1alpha, targeting it for proteasomal degradation. By decreasing HIF-alpha, SM-20 is thought to modulate the expression of hypoxia-regulated genes. SM-20 expression in the arterial wall is restricted to smooth muscle cells, which play it critical role in atherosclerosis and arterial injury. To further elucidate the regulation of SM-20 in smooth muscle, we cloned and analyzed the rat SM-20 promoter. In transient transfections, the SM-20 promoter displayed approximate to 6-fold greater activity in smooth Muscle cells vs. fibroblasts. Deletion analysis and electrophoretic mobility shift assays demonstrated that SM-20 transcription was regulated by two Spl/Sp3 sites. A shift ill binding to the Spl/Sp3 sites. a decrease in Sp1 and Sp3 protein levels. and the emergence of a lower molecular weight form of Sp1 were seen in serum-deprived or post-confluent SMC, suggesting that SM-20 is regulated during smooth muscle cell differentiation. (C) 2004 Elsevier Inc. All rights reserved.
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