Adiponectin promotes muscle regeneration through binding to T-cadherin View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Yoshimitsu Tanaka, Shunbun Kita, Hitoshi Nishizawa, Shiro Fukuda, Yuya Fujishima, Yoshinari Obata, Hirofumi Nagao, Shigeki Masuda, Yuto Nakamura, Yuri Shimizu, Ryohei Mineo, Tomoaki Natsukawa, Tohru Funahashi, Barbara Ranscht, So-ichiro Fukada, Norikazu Maeda, Iichiro Shimomura

ABSTRACT

Skeletal muscle has remarkable regenerative potential and its decline with aging is suggested to be one of the important causes of loss of muscle mass and quality of life in elderly adults. Metabolic abnormalities such as obesity were linked with decline of muscle regeneration. On the other hand, plasma levels of adiponectin are decreased in such metabolic conditions. However, plasma levels of adiponectin have been shown to inversely correlate with muscle mass and strength in elderly people especially with chronic heart failure (CHF). Here we have addressed whether adiponectin has some impact on muscle regeneration after cardiotoxin-induced muscle injury in mice. Muscle regeneration was delayed by angiotensin II infusion, mimicking aging and CHF as reported. Adiponectin overexpression in vivo decreased necrotic region and increased regenerating myofibers. Such enhanced regeneration by excess adiponectin was also observed in adiponectin null mice, but not in T-cadherin null mice. Mechanistically, adiponectin accumulated on plasma membrane of myofibers both in mice and human, and intracellularly colocalized with endosomes positive for a multivesicular bodies/exosomes marker CD63 in regenerating myofibers. Purified high-molecular multimeric adiponectin similarly accumulated intracellularly and colocalized with CD63-positive endosomes and enhanced exosome secretion in differentiating C2C12 myotubes but not in undifferentiated myoblasts. Knockdown of T-cadherin in differentiating C2C12 myotubes attenuated both adiponectin-accumulation and adiponectin-mediated exosome production. Collectively, our studies have firstly demonstrated that adiponectin stimulates muscle regeneration through T-cadherin, where intracellular accumulation and exosome-mediated process of adiponectin may have some roles. More... »

PAGES

16

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-37115-3

DOI

http://dx.doi.org/10.1038/s41598-018-37115-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111102199

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30626897


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