TRAF6 ensures health of stem cells and may lead to improved stem cell therapies for DMD and other muscle wasting diseases
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.
The research, published today in the Journal of Clinical Investigation, describes the role of TNF receptor-associated factor 6 (TRAF6), an adaptor protein and E3 ubiquitin ligase, in ensuring the vitality of stem cells that regenerate muscle tissue.
Specialized stem cells known as satellite cells reside in skeletal muscle in an inactive state. When muscle injury occurs, a complex chain of signals prompts the satellite cells to awaken and generate new muscle cells to repair the injury. Previous research had shown that Pax7 (a paired-box transcription factor) is essential to this regeneration. When Pax7 is missing or reduced, the satellite cells undergo premature differentiation, or lose their stem properties and their ability to regenerate injured muscles.
In their research, authors Sajedah M. Hindi, Ph.D., and Ashok Kumar, Ph.D., discovered that removing TRAF6 depletes Pax7, resulting in reduced muscle regeneration in both normal and Duchenne muscular dystrophy (DMD) mouse models.
Hindi, a post-doctoral fellow, and Kumar, professor and distinguished university scholar in UofL's Department of Anatomical Sciences and Neurobiology, believe this is because TRAF6 is upstream from Pax7 in the signaling process involved in muscle repair and orchestrates multiple signals controlling the muscle regeneration process.
"We have discovered a pathway by which the Pax7 and myogenic potential of satellite cells is regulated. The protein TRAF6 is a very important adaptor protein that is involved in multiple signaling pathways and its functions are important to maintain the stemness of satellite cells in adults," Kumar said.
"In normal conditions, skeletal muscle is a self-healing tissue and can recover promptly from most trauma because of the satellite cells. But in disease conditions like muscular dystrophies, satellite cells can't keep up with repeated cycles of injury and are ultimately exhausted or functionally impaired," Hindi said.
"Our next step is to see if this functional impairment is partially due to lack of TRAF6 signaling in satellite cells. If so, we are thinking we can take a patient's stem cells, restore the TRAF6 activity, put them back and boost their regenerative potential."
Kumar and Hindi believe their research ultimately will lead to improved treatments for muscle wasting diseases such as muscular dystrophy, ALS, cancer cachexia, diabetes, heart disease and others.
"Right now the problem in donor stem cell therapy is that we inject the stem cells into the patient but most of the stem cells don't proliferate very well, so they repair very little part of the muscle," Kumar said. "But if you have stem cells that are over expressing this protein TRAF6, they may proliferate longer and they may repair the muscle much more effectively."
Betty Coffman | EurekAlert!
Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News