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J Stem Cell Regen Biol. 2015 Nov 12;1(1):1-7.

Mice lacking MKP-1 and MKP-5 Reveal Hierarchical Regulation of Regenerative Myogenesis.

Author information

1
Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
2
Department of Pharmacology.
3
Department of Pharmacology; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract

The relative contribution 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/MKP 5-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.

KEYWORDS:

MAP kinase phosphatases; Macrophage function; Mitogen-activated protein kinase; Regenerative myogenesis; Signal transduction pathways

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