Lipopolysaccharide pretreatment promotes cardiac stem cell migration through heat shock protein 90-dependent β-catenin activation

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• 作者：Li Zhang^a ; Wei-Ran Geng^a ; Jue Hu^b ; Xiao-Ming Chen^c ; Yue-Liang Shen^a ; Lin-Lin Wang^d ; Jian-Ping Jiang^e ; ^{jianpingj@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Ying-Ying Chen^a ; ^{bchenyy@zju.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：LPS (PubChem CID ; 53481793) ; 17-AAG (PubChem CID ; 6440175) ; FH535 (PubChem CID ; 3463933)
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 May 2016
• 年：2016
• 卷：153
• 期：Complete
• 页码：132-140
• 全文大小：2048 K

文摘

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.

Main 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.

Key findings

Exposure of CSCs to higher LPS (1 μg/mL) for 24 h inhibited the cell migration. However, LPS (0.01, 0.1 μg/mL) significantly increased the number of migrated CSCs, which reached a peak at 0.01 μg/mL. LPS (0.01 μg/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.

Significance

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.