177 Psychosocial resources associated with lymphocyte terminal maturity in older men and women
Brain Behavior and Immunity(2021)
Abstract
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 MET and FAS, both encoding cell membrane signaling receptors.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, a 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 MET promoter. Activating p53 with nutlin3a further potentiated the suppression of MET 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 MET by cooperating with p53, and that Smad2 also activated FAS, a target gene of its transcription factor activity.Our study suggests a pro-apoptotic mechanism in human SMCs, whereby Smad2 negatively and positively regulates MET and FAS, genes encoding anti-apoptotic and pro-apoptotic factors, respectively.
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Key words
terminal maturity,lymphocyte,older men,psychosocial resources
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