Researchers discover key signaling protein for muscle growth

November 20, 2017 by Betty Coffman, University of Louisville
Skeletal muscle tissue. Credit: University of Michigan Medical School

Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., professor and distinguished university scholar in UofL's Department of Anatomical Sciences and Neurobiology, led a team of researchers who have described the protein's critical role in the growth and repair of skeletal muscles, both in post-natal development and in the regeneration of injured adult muscles.

UofL post-doctoral fellows Sajedah M. Hindi, Ph.D., and Yann S. Gallot, Ph.D., along with Jonghyun Shin, Ph.D., formerly of UofL and now with Yonsei University in South Korea, conducted the research in Kumar's lab. It is published today in Nature Communications.

In the formation of muscle, specialized progenitor or stem cells multiply. They then differentiate into preliminary muscle cells called myoblasts. The myoblasts fuse together and subsequently form muscle fiber. Using animal models, the UofL researchers worked with both neonatal cells and adult cells to determine that MyD88, a key signaling protein in the human body, is required in sufficient quantity for myoblasts to fuse.

Hindi believes that MyD88 eventually may be used to improve the effectiveness of therapies using donor cells for the treatment of degenerative muscle disorders such as muscular dystrophies.

"Since MyD88 promotes only the fusion of myoblasts without affecting their proliferation or differentiation, enhancing the levels of MyD88 levels could be a means to enhance engraftment of exogenous myoblasts in cellular therapies," Hindi said.

Kumar adds that increasing the expression of MyD88 could be used in the treatment of rhabdomyosarcomas, cancerous tumors that develop in skeletal muscles and often affect children.

"We are investigating whether augmenting the levels of MyD88 inhibits growth of rhabdomyosarcoma in animal models," Kumar said. "Finally, we are investigating whether the loss of MyD88 is responsible for the diminished muscle regeneration capacity in the elderly."

Research in Kumar's lab focuses on understanding the molecular and signaling mechanisms that regulate the acquisition and maintenance of skeletal muscle mass. For the past eight years, they have been investigating the proximal signaling mechanisms that regulate atrophy, regeneration and hypertrophy, in addition to the signaling mechanisms that regulate self-renewal and differentiation of satellite cells in myogenic lineage.

In 2015, research from Kumar and Hindi published in the Journal of Clinical Investigation described the role of TNF receptor-associated factor 6 (TRAF6) in maintaining satellite and their ability to regenerate injured muscles. Just ten days later, research from the lab published in Nature Communications revealed how the protein transforming growth factor-ß-activated kinase 1 (TAK1) is vital in the self-renewal of satellite .

Explore further: Scientists enhance understanding of muscle repair process

More information: Sajedah M. Hindi et al, MyD88 promotes myoblast fusion in a cell-autonomous manner, Nature Communications (2017). DOI: 10.1038/s41467-017-01866-w

Related Stories

Scientists enhance understanding of muscle repair process

December 9, 2015
In today's issue of Nature Communications, University of Louisville scientists reveal research that increases the understanding of the mechanisms regulating adult stem cells required for skeletal muscle regeneration. Sajedah ...

Scientists identify critical pathway to improve muscle repair

November 30, 2015
Researchers at the University of Louisville have discovered a mechanism involved in skeletal muscle repair that may enable clinicians to boost the effectiveness of adult stem cell therapies for diseases such as muscular dystrophy. ...

Researchers find key to muscle regeneration

June 14, 2017
Saint Louis University researchers report in Molecular Metabolism new findings that the nuclear receptor REV-ERB appears to play a key role in muscle regeneration, suggesting the receptor may be a good target for new drugs ...

Discovery of a 'conductor' in muscle development

February 25, 2014
A team led by Jean-François Côté, researcher at the IRCM, identified a ''conductor'' in the development of muscle tissue. The discovery, published online yesterday by the scientific journal Proceedings of the National ...

At the right place at the right time—new insights into muscle stem cells

September 17, 2012
Muscles have a pool of stem cells which provides a source for muscle growth and for regeneration of injured muscles. The stem cells must reside in special niches of the muscle for efficient growth and repair.

A stem cell gene found to command skeletal muscle regeneration

October 12, 2016
Prox1 gene has long been known to play an important role in fetal development. Finnish researchers have now discovered that Prox1 is essential also for skeletal muscle stem cell differentiation.

Recommended for you

Using light to stop itch

December 17, 2018
Itch is easily one of the most annoying sensations. For chronic skin diseases like eczema, it's a major symptom. Although it gives temporary relief, scratching only makes things worse because it can cause skin damage, additional ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.