Mice lacking MKP-Â1 and MKP-5 Reveal Hierarchical Regulation of Regenerative Myogenesis
Florian Gatzke2, Julia M. Molle1, Han Bin Lee1, Emma T. Helm1, Jessie J. Oldham1, Lei Zhang2, David E. Gerrard1, Anton M. Bennett2,3
Affiliation
- 1Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- 2Department of Pharmacology
- 3Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, Connecticut, USA
Corresponding Author
Dr. Hao Shi. Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University,304 Litton Reaves Hall, Blacksburg, Virginia 24060, USA; Tel: 1-540-231-9663; E-mail: haoshi@vt.edu
Citation
Shi, H., et al. Mice lacking MKP-1 and MKP-5 Reveal Hierarchical Regulation of Regenerative Myogenesis. (2015) J Stem Cell Regen Bio 1(1): 9- 15.
Copy rights
©2015 Shi, H. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Keywords
Abstract
The relative contributions of the MAP kinase phosphatases (MKPs) in the integration of MAP kinase-dependent signaling during regenerative myogenesis has yet to be fully investigated. MKP-1 and MKP-5 maintain skeletal muscle homeostasis by providing positive and negative effects on regenerative myogenesis, respectively. In order to define the hierarchical contributions of MKP-1 and MKP-5 in the regulation of regenerative myogenesis we genetically ablated both MKPs in mice. MKP-1/MKP5- deficient double-knockout (MKP1/5- DKO) mice were viable, and upon skeletal muscle injury, were severely impaired in their capacity to regenerate skeletal muscle. Satellite cells were fewer in number in MKP1/5-DKO mice and displayed a reduced proliferative capacity as compared with those derived from wild-type mice. MKP1/5-DKO mice exhibited increased inflammation and the macrophage M1 to M2 transition during the resolution of inflammation was impaired following injury. These results demonstrate that the actions of MKP-1 to positively regulate myogenesis predominate over those of MKP-5, which negatively regulates myogenesis. Hence, MKP-1 and MKP-5 function to maintain skeletal muscle homeostasis through non-overlapping and opposing signaling pathways.
