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!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Information Technology
05.12.2016 | Earth Sciences