title: Heat shock protein 90 stimulates rat mesenchymal stem cell migration via PI3K/Akt and ERK1/2 pathways.
abstract: The objective of this study was to determine the role of Hsp90α in regulating the migration of mesenchymal stem cells (MSCs) and to investigate the underlying mechanisms of this effect. MSCs migration was assessed by wound healing assay and transwell migration assay. Hsp90α expression was silenced in MSC by siRNA (sirHsp90α). The activity of secreted metalloproteases MMP-2 and MMP-9, and their expression levels in MSC were evaluated using gelatin zymography, Western blot analysis and real-time PCR. Gene expression of VCAM-1 and CXCR4 cytokines was evaluated by real-time PCR. Akt and ERK activity were analyzed by Western blotting using antibodies against phosphorylated forms of these proteins. Treatment with Hsp90α significantly enhanced MSC migration, and this effect was blocked by transfecting MSC with sirHsp90α. Treating the cells with recombinant human Hsp90α (rhHsp90α) enhanced gene expression and protein levels of MMP-2 and MMP-9, as well as their secretion and activity. MSC incubated with rhHsp90α exhibited increased gene expression of CXCR4 and VCAM-1. Finally, the levels of phosphorylated Akt and Erk were markedly increased by rhHsp90α treatment. These findings indicate that Hsp90α promotes MSCs migration via PI3K/Akt and ERK signaling pathways, and that this effect is possibly mediated by MMPs, SDF-1/CXCR4 pathway, and VCAM-1.
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310009, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Xinyang
authors.initials: X
authors.lastname: Hu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xie
authors.forename: Xianbao
authors.initials: X
authors.lastname: Liu
authors.forename: Jianan
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: C486264:Cxcr4 protein, rat; D018841:HSP90 Heat-Shock Proteins; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9