Transforming Growth Factor β-regulated MicroRNA-29a Promotes Angiogenesis through Targeting the Phosphatase and Tensin Homolog in Endothelium

The TGF-beta pathway plays an important role in physiological and pathological angiogenesis. MicroRNAs (miRNAs) are a class of 18- to 25-nucleotide, small, noncoding RNAs that function by regulating gene expression. A number of miRNAs have been found to be regulated by the TGF-beta pathway. However, the role of endothelial miRNAs in the TGF-beta-mediated control of angiogenesis is still largely unknown. Here we investigated the regulation of endothelial microRNA-29a (miR-29a) by TGF-beta signaling and the potential role of miR-29a in angiogenesis. MiR-29a was directly up-regulated by TGF-beta/Smad4 signaling in human and mice endothelial cells. In a chick chorioallantoic membrane assay, miR-29a overexpression promoted the formation of new blood vessels, and miR-29a suppression completely blocked TGF-beta 1-stimulated angiogenesis. Consistently, miR-29a overexpression increased tube formation and migration in endothelial cultures. Mechanistically, miR-29a directly targeted the 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-beta-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity.