Relaxin regulates MMP expression and promotes satellite cell mobilization during muscle healing in both young and aged mice.

Abstract

The polypeptide hormone relaxin has been proven to be effective in promoting both the remodeling and regeneration of various tissues, including cardiac muscle. In addition, our previous study demonstrated that relaxin is beneficial to skeletal muscle healing by both promoting muscle regeneration and preventing fibrosis formation. However, the molecular and cellular mechanisms of relaxin in regulating both myogenic cell differentiation and muscle healing process are still unclear. In this study, C2C12 mouse myoblasts and primary human myoblasts were treated with relaxin to investigate its potential effect in vitro; relaxin was also injected intramuscularly into the injured site of the mouse on the second day after injury to observe its function in vivo, especially in the aged muscle. Results showed that relaxin promoted myogenic differentiation, migration, and activation of matrix metalloproteinases (MMPs) of cultured myoblasts in vitro. In the injured muscle, relaxin administration promoted the activation of Pax7-positive skeletal muscle satellite cells and increased its local population compared with nontreated control muscles. Meanwhile, both angiogenesis and revascularization were increased, while the extended inflammatory reaction was repressed in the relaxin-treated injured muscle. Moreover, relaxin similarly promoted muscle healing in mice with aged muscle. These results revealed the multiple effects of relaxin in systematically improving muscle healing as well as its potential for clinical applications in patients with skeletal muscle injuries and diseases.

• Authors: Xiaodong Mu, Maria L Urso, Kiley Murray, Freddie Fu, Yong Li
• Journal: The American journal of pathology (Am J Pathol) Vol. 177 Issue 5 Pg. 2399-410 (Nov 2010) ISSN: 1525-2191 [Electronic] United States
• PMID: 20934971 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Isoenzymes
• PAX7 Transcription Factor
• Relaxin
• Matrix Metalloproteinases

Topics

• Aging (physiology)
• Animals
• Cell Line
• Cell Movement
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Enzyme Activation
• Humans
• Isoenzymes (genetics, metabolism)
• Male
• Matrix Metalloproteinases (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Muscle, Skeletal (drug effects, injuries, physiology)
• Neovascularization, Physiologic
• PAX7 Transcription Factor (metabolism)
• Regeneration (drug effects, physiology)
• Relaxin (pharmacology)
• Satellite Cells, Skeletal Muscle (drug effects, metabolism)
• Wound Healing (drug effects)