Heat Shock Protein 90 Stimulates Rat Mesenchymal Stem Cell Migration via PI3K/Akt and ERK1/2 Pathways

被引:52
作者
Gao, Feng [1 ,2 ,3 ]
Hu, Xinyang [1 ,2 ]
Xie, Xiaojie [1 ,2 ]
Liu, Xianbao [1 ,2 ]
Wang, Jianan [1 ,2 ]
机构
[1] Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Cardiol, Hangzhou 310009, Zhejiang, Peoples R China
[2] Zhejiang Univ, Coll Med, Affiliated Hosp 2, Cardiovasc Key Lab Zhejiang Prov, Hangzhou 310009, Zhejiang, Peoples R China
[3] Zhejiang Prov Peoples Hosp, Dept Cardiol, Hangzhou 310014, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Heat shock protein; Mesenchymal stem cell; Migration; Cytokines; FACTOR-I; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; INHIBITS PROLIFERATION; HSP90; ANTAGONIST; BONE; DIFFERENTIATE; REPAIR; FORMS; NEOVASCULARIZATION;
D O I
10.1007/s12013-014-0228-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The objective of this study was to determine the role of Hsp90 alpha 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. Hsp90 alpha expression was silenced in MSC by siRNA (sirHsp90 alpha). 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 Hsp90 alpha significantly enhanced MSC migration, and this effect was blocked by transfecting MSC with sirHsp90 alpha. Treating the cells with recombinant human Hsp90 alpha (rhHsp90 alpha) enhanced gene expression and protein levels of MMP-2 and MMP-9, as well as their secretion and activity. MSC incubated with rhHsp90 alpha exhibited increased gene expression of CXCR4 and VCAM-1. Finally, the levels of phosphorylated Akt and Erk were markedly increased by rhHsp90 alpha treatment. These findings indicate that Hsp90 alpha 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.
引用
收藏
页码:481 / 489
页数:9
相关论文
共 42 条
[1]
Stromal cell-derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury [J].
Abbott, JD ;
Huang, Y ;
Liu, D ;
Hickey, R ;
Krause, DS ;
Giordano, FJ .
CIRCULATION, 2004, 110 (21) :3300-3305
[2]
The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques [J].
Abi-Younes, S ;
Sauty, A ;
Mach, F ;
Sukhova, GK ;
Libby, P ;
Luster, AD .
CIRCULATION RESEARCH, 2000, 86 (02) :131-138
[3]
Mesenchymal stem cell interactions with growth factors on kidney repair [J].
Baer, Patrick C. ;
Geiger, Helmut .
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2010, 19 (01) :1-6
[4]
Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium - Feasibility, cell migration, and body distribution [J].
Barbash, IM ;
Chouraqui, P ;
Baron, J ;
Feinberg, MS ;
Etzion, S ;
Tessone, A ;
Miller, L ;
Guetta, E ;
Zipori, D ;
Kedes, LH ;
Kloner, RA ;
Leor, J .
CIRCULATION, 2003, 108 (07) :863-868
[5]
Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function [J].
Basso, AD ;
Solit, DB ;
Chiosis, G ;
Giri, B ;
Tsichlis, P ;
Rosen, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39858-39866
[6]
Role of α4 integrin and VCAM-1 in CD18-independent neutrophil migration across mouse cardiac endothelium [J].
Bowden, RA ;
Ding, ZM ;
Donnachie, EM ;
Petersen, TK ;
Michael, LH ;
Ballantyne, CM ;
Burns, AR .
CIRCULATION RESEARCH, 2002, 90 (05) :562-569
[7]
Human Multipotent Adipose-Derived Stem Cells Differentiate into Functional Brown Adipocytes [J].
Elabd, Christian ;
Chiellini, Chiara ;
Carmona, Mamen ;
Galitzky, Jean ;
Cochet, Olivia ;
Petersen, Rasmus ;
Penicaud, Luc ;
Kristiansen, Karsten ;
Bouloumie, Anne ;
Casteilla, Louis ;
Dani, Christian ;
Ailhaud, Gerard ;
Amri, Ez-Zoubir .
STEM CELLS, 2009, 27 (11) :2753-2760
[8]
Bone Marrow Stem Cells for the Treatment of Ischemic Heart Disease: A Clinical Trial Review [J].
Fuh, Eric ;
Brinton, Todd J. .
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, 2009, 2 (02) :202-218
[9]
Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways [J].
Gao, Feng ;
Hu, Xin-yang ;
Xie, Xiao-jie ;
Xu, Qi-yuan ;
Wang, Ya-ping ;
Liu, Xian-bao ;
Xiang, Mei-xiang ;
Sun, Yong ;
Wang, Jian-an .
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B, 2010, 11 (08) :608-617
[10]
Giaccone G, 2009, CELL CYCLE, V8, P2682