title: Acetylcholine induces mesenchymal stem cell migration via Ca2+ /PKC/ERK1/2 signal pathway.
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.
authors.affiliation: Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Hubei 442000, China. tangjm416@163.com
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Kong
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Lin-Yun
authors.initials: LY
authors.lastname: Guo
authors.forename: Yong-Hang
authors.initials: YH
authors.lastname: Huang
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Yang
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011976:Receptors, Muscarinic; D011493:Protein Kinase C; D000109:Acetylcholine; D002118:Calcium