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Acetylcholine induces mesenchymal stem cell migration via Ca2+ /PKC/ERK1/2 signal pathway
Authors:Tang Jun-Ming  Yuan Jie  Li Qing  Wang Jia-Ning  Kong Xia  Zheng Fei  Zhang Lei  Chen Long  Guo Lin-Yun  Huang Yong-Hang  Yang Jian-Ye  Chen Shi-You
Institution:Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Hubei 442000, China. tangjm416@163.com
Abstract:Acetylcholine (ACh) plays an important role in neural and non-neural function, but its role in mesenchymal stem cell (MSC) migration remains to be determined. In the present study, we have found that ACh induces MSC migration via muscarinic acetylcholine receptors (mAChRs). Among several mAChRs, MSCs express mAChR subtype 1 (m1AChR). ACh induces MSC migration via interaction with mAChR1. MEK1/2 inhibitor PD98059 blocks ERK1/2 phosphorylation while partially inhibiting the ACh-induced MSC migration. InsP3Rs inhibitor 2-APB that inhibits MAPK/ERK phosphorylation completely blocks ACh-mediated MSC migration. Interestingly, intracellular Ca(2+) ATPase-specific inhibitor thapsigargin also completely blocks ACh-induced MSC migration through the depletion of intracellular Ca(2+) storage. PKCα or PKCβ inhibitor or their siRNAs only partially inhibit ACh-induced MSC migration, but PKC-ζ siRNA completely inhibits ACh-induced MSC migration via blocking ERK1/2 phosphorylation. These results indicate that ACh induces MSC migration via Ca(2+), PKC, and ERK1/2 signal pathways.
Keywords:ACETYLCHOLINE  MUSCARINIC RECEPTORS  MESENCHYMAL STEM CELL  MIGRATION  PKC  ERK1/2  CALCIUM
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