AI Article Synopsis
- Vascular smooth muscle cell (SMC) apoptosis plays a key role in cardiovascular diseases, and the study focuses on the role of Smad2, a transcription factor linked to aortic aneurysm.
- Using microarray analysis, the research identified that Smad2 regulates the expression of two significant genes: it promotes the anti-apoptotic gene Met and represses the pro-apoptotic gene Fas.
- The findings suggest a mechanism where Smad2 works with p53 to regulate these genes, highlighting its role in controlling SMC apoptosis and potentially contributing to cardiovascular disease progression.
Article Abstract
Background: Vascular smooth muscle cell (SMC) apoptosis is involved in major cardiovascular diseases. Smad2 is a transcription factor implicated in aortic aneurysm. The molecular mediators of Smad2-driven SMC apoptosis are not well defined. Here we have identified a Smad2-directed mechanism involving and , both encoding cell membrane signaling receptors.
Methods And Results: Guided by microarray analysis in human primary aortic SMCs, loss/gain-of-function (siRNA/overexpression) indicated that Smad2 negatively and positively regulated, respectively, the gene expression of Met which was identified herein as anti-apoptotic and that of Fas, known pro-apoptotic factor. While co-immunoprecipitation suggested a physical association of Smad2 with p53, chromatin immunoprecipitation followed by quantitative PCR revealed their co-occupancy in the same region of the promoter. Activating p53 with nutlin3a further potentiated the suppression of promoter-dependent luciferase activity and the exacerbation of SMC apoptosis that were caused by Smad2 overexpression. These results indicated that Smad2 in SMCs repressed the transcription of by cooperating with p53, and that Smad2 also activated , a target gene of its transcription factor activity.
Conclusions: Our study suggests a pro-apoptotic mechanism in human SMCs, whereby Smad2 negatively and positively regulates , genes encoding anti-apoptotic and pro-apoptotic factors, respectively.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017589 | PMC |
| http://dx.doi.org/10.1016/j.athplu.2021.08.005 | DOI Listing |
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