COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation

Seock Won Youn, Hyun Chae Lee, Sae Won Lee, Jaewon Lee, Hyunduk Jang, Eun Ju Lee, Hyo Soo Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Angiopoietin-1 modulates vascular stability via Tie2 on endothelial cells. In our previous study, we also showed it acts as an inhibitor of cardiomyocyte death. However, it remains poorly understood how Ang1 regulates myogenesis during muscle regeneration. Here we found that COMP-Ang1 (cAng1) enhances muscle regeneration through N-cadherin activation. Muscle fiber regeneration after limb muscle damage by ischemic injury was enhanced with cAng1 treatment. Mechanistically cAng1 directly bound to N-cadherin on the myoblast surface in a Ca2+ dependent manner. The interaction enhanced N-cadherin activation via N-cadherin/p120-catenin complex formation, which in turn activated p38MAPK (but not AKT or ERK) and myogenin expression (but not myoD) as well as increasing myogenin+ cells in/ex vivo. After transplantation of GFP-expressing myoblasts (GFP-MB), we showed an increased generation of GFP+ myotubes with adenovirus cAng1 (Adv-cAng1) injection. Adv-cAng1, however, could not stimulate myotube formation in N-cadherin-depleted GFP-MB. Taken together, this study uncovers the mechanism of how cAng1 promotes myoblast differentiation and muscle regeneration through the N-cadherin/p120-catenin/p38MAPK/myogenin axis.

Original languageEnglish (US)
Article number12323
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Angiopoietin-1
Cadherins
Regeneration
Myoblasts
Myogenin
Muscles
Skeletal Muscle Fibers
Adenoviridae
Muscle Development
Cardiac Myocytes
Blood Vessels
Extremities
Endothelial Cells
Transplantation
Injections
Wounds and Injuries

ASJC Scopus subject areas

  • General

Cite this

Youn, S. W., Lee, H. C., Lee, S. W., Lee, J., Jang, H., Lee, E. J., & Kim, H. S. (2018). COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation. Scientific Reports, 8(1), [12323]. https://doi.org/10.1038/s41598-018-30513-7

COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation. / Youn, Seock Won; Lee, Hyun Chae; Lee, Sae Won; Lee, Jaewon; Jang, Hyunduk; Lee, Eun Ju; Kim, Hyo Soo.

In: Scientific Reports, Vol. 8, No. 1, 12323, 01.12.2018.

Research output: Contribution to journalArticle

Youn, SW, Lee, HC, Lee, SW, Lee, J, Jang, H, Lee, EJ & Kim, HS 2018, 'COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation', Scientific Reports, vol. 8, no. 1, 12323. https://doi.org/10.1038/s41598-018-30513-7
Youn, Seock Won ; Lee, Hyun Chae ; Lee, Sae Won ; Lee, Jaewon ; Jang, Hyunduk ; Lee, Eun Ju ; Kim, Hyo Soo. / COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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