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sonic hedgehog protein promotes bone marrow-derived endothelial pro-genitor cell proliferation,migration and VEGF production via PI 3-kinase/Akt signaling pathways

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Acta Pharmacologica Sinica 2006年第6期27卷 685-693页

作者： Jin-rong FU~2 Wen-li LIU~(2,4)Jian-feng ZHOU~2 Han-ying SUN~2 Hui-zhen XU~2 Li LUO~2 Heng ZHANG~2 Yu-feng ZHOU~3 2 Department of Hematology.Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China:3 Department of Pediatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China Department of Hematology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

Aim:To investigate the effects of sonic hedgehog(shh)protein on bone marrow-derived endothelial progenitor cells(BM-EPC)proliferation,migration and vascu-lar endothelial growth factor(VEGF)production,and the potential signaling path-ways involved in these ***:Bone marrow-derived Flk-1~+ cells wereenriched using the MACS system from adult Kunming mice and then BM-EPCwas cultured in gelatin-coated culture *** effects of shh N-terminal pep-tide on BM-EPC proliferation were evaluated using the MTT colorimetric *** migration was assayed using a modified Boyden chamber *** of VEGF was determined by ELISA and immunofluorescence *** potential involvement of PKC and PI3K signaling pathways was exploredusing selective inhibitor or Western ***:The proliferation,migrationand VEGF production in BM-EPC could be promoted by endogenous shh N-terminal peptide at concentrations of 0.1μg/mL to 10 μg/mL,and could be inhib-ited by anti-shh ***-mediated proliferation and migration in BM-EPCcould be partly attenuated by ***-PI3-kinase expression in newlyseparated BM-EPC was low,and it increased significantly when exogenous shhN-terminal peptide was added,but could be attenuated by anti-human/mouse shhN-terminal peptide ***,the inhibitor of the PI3-kinase,but notthe inhibitor of the PKC,significantly inhibited the shh-mediated proliferation,migration and VEGF ***:Shh protein can stimulate bonemarrow-derived BM-EPC proliferation,migration and VEGF production,whichmay promote neovascularization to ischemic *** results also suggeststhat the PI3-kinase/Akt signaling pathways are involved in the angiogenic effectsof shh.

关键词： mouse sonic hedgehog protein endothelial cells stem cells protein kinase C 1-phosphatidylinositol 3-kinase vascular endothelial growth factor A cell proliferation emigration immigration

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