title: IL-1β-Induced Mesenchymal Stem Cell Migration Involves MLCK Activation via PKC Signaling.
abstract: Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury, possibly attracted by inflammatory cytokines. Although many cytokines can induce stem cell migration, the underlying mechanism is not fully understood. We found that tail vein-injected MSCs migrate to the pancreas in nonobese diabetic (NOD) mice. An ELISA assay revealed that hyperglycemic NOD mice have higher pancreatic levels of interleukin-1β (IL-1β) than normal NOD mice and that IL-1β stimulates MSC migration in a Transwell assay and electric cell-substrate impedance sensing system. Microarray analysis showed that myosin light chain kinase (MLCK) is involved in IL-1β-induced MSC migration, while Western blots showed that IL-1β stimulates MLCK expression and activation and that MLCK-siRNA transfection reduces MSC migration. Kinase inhibitors, chromatin immunoprecipitation, and a knockdown study revealed that IL-1β-induced MLCK expression is regulated by the PKCδ/NF-κB signaling pathway, and a kinase inhibitor study revealed that IL-1β-induced MLCK activation occurs via the PKCα/MEK/ERK signaling pathway. These results show that IL-1β released from the pancreas of hyperglycemic NOD mice induces MSC migration and that this is dependent on MLCK expression via the PKCδ/NF-κB pathway and on MLCK activation via the PKCα/MEK/ERK signaling cascade. This study increases our understanding of the mechanisms by which MSCs home to injury sites.
authors.affiliation: Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Zu
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Yang
authors.forename: Pei-Jiun
authors.initials: PJ
authors.lastname: Tsai
authors.forename: Jia-Fwu
authors.initials: JF
authors.lastname: Shyu
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
authors.forename: Zen-Chung
authors.initials: ZC
authors.lastname: Weng
authors.forename: Tien-Hua
authors.initials: TH
authors.lastname: Chen
authors.forename: Hwai-Shi
authors.initials: HS
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase