Visfatin exerts angiogenic effects on human umbilical vein endothelial cells through the mTOR signaling pathway

Joo Won Park, Won Ho Kim, So Hee Shin, Ji Yeon Kim, Mi Ran Yun, Keon Jae Park, Hyun Young Park

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The biologically active factors known as adipocytokines are secreted primarily by adipose tissues and can act as modulators of angiogenesis. Visfatin, an adipocytokine that has recently been reported to have angiogenic properties, is upregulated in diabetes, cancer, and inflammatory diseases. Because maintenance of an angiogenic balance is critically important in the management of these diseases, understanding the molecular mechanism by which visfatin promotes angiogenesis is very important. In this report, we describe our findings demonstrating that visfatin stimulates the mammalian target of the rapamycin (mTOR) pathway, which plays important roles in angiogenesis. Visfatin induced the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor (VEGF) in human endothelial cells. Inhibition of the mTOR pathway by rapamycin eliminated the angiogenic and proliferative effects of visfatin. The visfatin-induced increase in VEGF expression was also eliminated by RNA interference-mediated knockdown of the 70-kDa ribosomal protein S6 kinase (p70S6K), a downstream target of mTOR. Visfatin inactivated glycogen synthase kinase 3β (GSK3β) by phosphorylating it at Ser-9, leading to the nuclear translocation of β-catenin. Both rapamycin co-treatment and p70S6K knockdown inhibited visfatin-induced GSK3β phosphorylation at Ser-9 and nuclear translocation of β-catenin. Taken together, these results indicate that mTOR signaling is involved in visfatin-induced angiogenesis, and that this signaling leads to visfatin-induced VEGF expression and nuclear translocation of β-catenin. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number5
StatePublished - May 2011

Bibliographical note

Funding Information:
This study was supported by a Korean National Institute of Health intramural research grant (no. 2010-N63003-00 ).


  • Adipocytokine
  • Angiogenesis
  • GSK3β
  • MTOR
  • Visfatin


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