IL-1­β-induced mesenchymal stem cell migration involves MLCK activation via PKC signaling

Cheng Yu Lin, Chia Hua Zu, Chih Chang Yang, Pei Jiun Tsai, Jia Fwu Shyu, Chie Pein Chen, Zen Chung Weng, Tien Hua Chen, Hwai Shi Wang

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2011-2028
Number of pages18
JournalCell Transplantation
Volume24
Issue number10
DOIs
Publication statusPublished - Oct 13 2015

Keywords

  • Interleukin-1β (IL-1β)
  • Myosin light chain kinase (MLCK)
  • Nonobese diabetic (NOD) mice
  • Protein kinase C (PKC) signaling
  • Stem cell migration

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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  • Cite this

    Lin, C. Y., Zu, C. H., Yang, C. C., Tsai, P. J., Shyu, J. F., Chen, C. P., Weng, Z. C., Chen, T. H., & Wang, H. S. (2015). IL-1­β-induced mesenchymal stem cell migration involves MLCK activation via PKC signaling. Cell Transplantation, 24(10), 2011-2028. https://doi.org/10.3727/096368914X685258