Lee Chang Hee, Lee Mi-Sook, Kim Sun-Jin, Je Young-Tae, Ryu Sung Ho, Lee Taehoon
SIGMOL Institute of Molecular Medicine, SIGMOL Inc., 790-834 Pohang, South Korea.
Peptides. 2009 Feb;30(2):409-18. doi: 10.1016/j.peptides.2008.10.003. Epub 2008 Oct 17.
A novel synthetic hexapeptide (SFKLRY-NH(2)) that displays angiogenic activity has been identified by positional scanning of a synthetic peptide combinatorial library (PS-SPCL). The peptide induced proliferation, migration, and capillary-like tube formation in primary cultured HUVECs, and augmented vessel sprouting ex vivo while attenuated by the treatment with pertussis toxin (PTX) or U73122 (PLC-inhibitor) suggesting the influence of PTX-sensitive G-proteins and PLC. In addition, SFKLRY-NH(2) up-regulated the expression of VEGF-A in HUVECs and the neutralizing antibody against VEGF suppressed SFKLRY-NH(2)-induced tube formation activity. Taken together, these results suggest that SFKLRY-NH(2) may induce blood vessel formation by PTX-sensitive G protein-coupled receptor-PLC-Ca(2+) signaling cascade leading into VEGF-A expression in HUVECs.
通过合成肽组合文库的位置扫描(PS-SPCL)鉴定出一种具有血管生成活性的新型合成六肽(SFKLRY-NH(2))。该肽在原代培养的人脐静脉内皮细胞(HUVECs)中诱导增殖、迁移和毛细血管样管形成,并在体外增强血管芽生,而百日咳毒素(PTX)或U73122(磷脂酶C抑制剂)处理可减弱这种作用,提示PTX敏感的G蛋白和磷脂酶C的影响。此外,SFKLRY-NH(2)上调HUVECs中VEGF-A的表达,抗VEGF中和抗体抑制SFKLRY-NH(2)诱导的管形成活性。综上所述,这些结果表明SFKLRY-NH(2)可能通过PTX敏感的G蛋白偶联受体-磷脂酶C-Ca(2+)信号级联诱导血管形成,进而导致HUVECs中VEGF-A的表达。