P53 Promotes Retinoid Acid-induced Smooth Muscle Cell Differentiation by Targeting Myocardin
Abstract
TP53 is a widely studied tumor suppressor gene that controls various cellular functions, including cell differentiation. However, little is known about its functional roles in smooth muscle cells (SMCs) differentiation from embryonic stem cells (ESCs). SMC differentiation is at the heart of our understanding of vascular development, normal blood pressure homeostasis, and the pathogenesis of vascular diseases such as atherosclerosis, hypertension, restenosis, as well as aneurysm. Using retinoid acid (RA)-induced SMC differentiation models, we observed that p53 expression is increased during in vitro differentiation of mouse ESCs into SMCs. Meanwhile, suppression of p53 by shRNA reduced RA-induced SMC differentiation. Mechanistically, we have identified for the first time that Myocardin, a transcription factor that induces muscle cell differentiation and muscle-specific gene expression, is the direct target of p53 by bioinformatic analysis, luciferase reporter assay, and chromatin immunoprecipitation approaches. Moreover, in vivo SMC-selective p53 transgenic overexpression inhibited injury-induced neointimal formation. Taken together, our data demonstrate that p53 and its target gene, Myocardin, play regulatory roles in SMC diffe...Continue Reading
References
Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Aneurysm
Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.