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MICE LACKING MKP-?1 AND MKP-?5 REVEAL HIERARCHICAL REGULATION OF REGENERATIVE MYOGENESIS

Journal: Journal of Stem Cell and Regenerative Biology (Vol.1, No. 1)

Publication Date:

Authors : ;

Page : 1-7

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

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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.

Last modified: 2017-01-10 13:26:56