期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 15, 页码 10418-10426出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.444463
关键词
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资金
- Chinese National Key Program on Basic Research [2012CB945103, 2011CB964803, 2011CB504202]
- National Natural Science Foundation of China [31030040, 31171410]
- State Key Laboratory of Proteomics [SKLP-K201102]
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.
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