TGF-β Regulated miR-29a Promotes Angiogenesis through Targeting PTEN in Endothelium
نویسندگان
چکیده
The transforming growth factor-β (TGF-β) pathway plays important role in physiological and pathological angiogenesis. MicroRNAs (miRNAs) are a class of 18-25 nucleotides small noncoding RNAs that function by regulating gene expression. Numbers of miRNAs have been found to be regulated by TGF-β pathway. However, the role of endothelial miRNAs in the TGF-β-mediated control of angiogenesis is still largely unknown. Here we investigated the regulation of endothelial microRNA-29a (miR-29a) by TGF-β signaling and the potential role of miR-29a in angiogenesis. miR-29a was directly up-regulated by TGF-β/Smad4 signaling in human and mice endothelial cells. In chick chorioallantoic membrane assay, miR-29a overexpression promoted the formation of new blood vessels and miR-29a suppression completely blocked TGF-β1-stimulated angiogenesis. Consistently, miR-29a overexpression increased tube formation and migration in endothelial cultures. Mechanistically, miR-29a directly targeted phosphatase and tensin homolog (PTEN) in endothelial cells, leading to activation of the AKT pathway. PTEN knockdown recapitulated the role of miR-29a in endothelial migration, whereas AKT inhibition completely attenuated the stimulating role of miR-29a in angiogenesis. Taken together, these results reveal a crucial role of a TGF-β-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity. http://www.jbc.org/cgi/doi/10.1074/jbc.M112.444463 The latest version is at JBC Papers in Press. Published on February 20, 2013 as Manuscript M112.444463
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