title: Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium.
abstract: The TGF-β 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-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 a 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 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-β-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity.
authors: State Key Laboratory of Proteomics, Institute of Biotechnology, Beijing 100071, China.
authors: Jun
authors: J
authors: Wang
authors: Youliang
authors: Y
authors: Wang
authors: Yu
authors: Y
authors: Wang
authors: Ying
authors: Y
authors: Ma
authors: Yu
authors: Y
authors: Lan
authors: Xiao
authors: X
authors: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C547014:MIRN29 microRNA, mouse; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse