Lipopolysaccharide pretreatment promotes cardiac stem cell migration through heat shock protein 90-dependent β-catenin activation.
OBJECTIVE
To investigate the effect of lipopolysaccharide (LPS) on the migration of cardiac stem cells (CSCs) and whether β-catenin is involved in its underlying mechanism.


METHODS
CSCs were isolated from neonatal Sprague-Dawley rat hearts. Migration was detected using 24-well transwell system in vitro cultured CSCs and using carboxyfluorescein diacetate (CFDA)-labelled method in myocardial infarction rat model. The expression of toll like receptor 4 (TLR4), β-catenin, heat shock protein 90 (HSP90) was analyzed using western blotting.


RESULTS
Exposure of CSCs to higher LPS (1μg/mL) for 24h inhibited the cell migration. However, LPS (0.01, 0.1μg/mL) significantly increased the number of migrated CSCs, which reached a peak at 0.01μg/mL. LPS (0.01μg/mL) pretreatment promoted the migration of CFDA-labeled CSCs into the risk area in ischemia-reperfusion rat heart. And injection of LPS-pretreated CSCs also caused a significant decrease in infarct size when compared with LPS-untreated CSCs group. Lower dose of LPS did not influence the expression of TLR4 and total β-catenin protein. However, it enhanced the levels of active β-catenin, nuclear β-catenin, and HSP90 protein. Compared with LPS group, after preincubated with HSP90 inhibitor 17-AAG, the LPS-induced enhancement of active β-catenin protein and nuclear β-catenin protein was abolished. In addition, 17-AAG also prevented the lower dose of LPS-induced cell migration.


CONCLUSIONS
The results suggested that low dose of LPS pretreatmemt induced increased CSC migration, reduced the infarct size of ischemia-reperfusion heart. The mechanism might be due to the activation and translocation of β-catenin via HSP90-dependent manner.
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Li
L
Zhang
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Wei-Ran
WR
Geng
Department of Pharmacology, Zhejiang Medical College, Hangzhou 310053, China.
Jue
J
Hu
Department of Physiology, Medical School of Jinhua Polytechnic, Jinhua 321007, China.
Xiao-Ming
XM
Chen
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Yue-Liang
YL
Shen
Center for Stem Cell and Tissue Engineering, Zhejiang University School of Medicine, Hangzhou 310058, China.
Lin-Lin
LL
Wang
Department of Clinical Medicine, Zhejiang, Medical College, Hangzhou 310053, China. Electronic address: jianpingj@gmail.com.
Jian-Ping
JP
Jiang
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: bchenyy@zju.edu.cn.
Ying-Ying
YY
Chen
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; D008070:Lipopolysaccharides; D051176:beta Catenin
17-AAG (PubChem CID: 6440175); Cardiac stem cells; FH535 (PubChem CID: 3463933); Heat shock protein 90; LPS (PubChem CID: 53481793); Lipopolysaccharide; Migration; β-Catenin