title: HGF expression induced by HIF-1α promote the proliferation and tube formation of endothelial progenitor cells.
abstract: Hypoxia-inducible factor-1α (HIF-1α) and hepatocyte growth factor (HGF) play important roles in postnatal neovascularization. However, the interaction of these two pathways is not fully understood. The present study utilized CoCl(2) treated-endothelial progenitor cells (EPCs) (EPCs exposure to CoCl(2) are under mimic hypoxia) to examine the expressions of HIF-1α and HGF and futher to assess whether or not the inhibitor (2-methoxyestradiol [2ME2]) of HIF-1α decrease the HGF expression. In addition, to investigate the effects of HGF on the proliferation and tube formation of EPCs under mimic hypoxia, EPCs were transfected with NK4 (HGF antagonist) plasmid and exposed to CoCl(2), then the proliferation of these EPCs was assayed by MTS and the tube formation capacity of these EPCs on Matrigel was detected. The analysis indicated that CoCl(2) treatment induced HIF-1α expression of EPCs, and futher promoted HGF expression. While after 2ME2 was used in CoCl(2) treated-EPCs, HGF expression was markedly inhibited compared with non-pretreated EPCs with 2ME2, which also showed that HGF expression in EPCs was mediated by HIF-1α. Further, the results showed that after EPCs were transfected with NK4 in spite of being exposed to CoCl(2), their proliferation activity and tube formation capacity were weakened, which in turn indicated that HGF could promote the proliferation and the tube formation of EPCs, and this process might be regulated by HIF-1α.
authors.affiliation: Department of Urinary Surgery, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Zhan
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Sufen
authors.initials: S
authors.lastname: Guo
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000209:etiology; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D018039:Receptors, Tachykinin / Q000235:genetics / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007797:Laminin; D011509:Proteoglycans; D018039:Receptors, Tachykinin; C102505:neurokinin receptor 4; C059485:matrigel; D003035:Cobalt; D004958:Estradiol; D017228:Hepatocyte Growth Factor; D000077584:2-Methoxyestradiol; D003094:Collagen; C018021:cobaltous chloride
keywords: endothelial progenitor cells; hepatocyte growth factor; hypoxia-inducible factors-1α; proliferation; tube formation