Aaron Barchowsky, Ph.D.
University of Pittsburgh
R01ES023696, R01ES013781, F32ES022134
Researchers, funded by NIEHS, have found that chronic exposure to arsenic may alter the ability of muscles to regenerate after injury. They also found that a protein involved in tissue repair, called NF kappa B, may play a role. According to the authors, these findings may aid in the development of strategies to prevent or reverse the effects of arsenic on muscle regeneration.
The researchers exposed mice to arsenic in their drinking water for five weeks, which compares to about two human years, then injured muscle and compared the outcomes in the exposed and unexposed mice. They found a significant decrease in muscle regeneration and functional recovery in mice exposed to arsenic. They also observed structural differences in the muscle tissue surrounding muscle cells, or extracellular matrix.
The researchers then seeded the arsenic-exposed extracellular matrix with human muscle stem cells, which are normally activated after muscle injury to restore damaged muscle tissue. They found that the arsenic-exposed extracellular matrix lowered the ability of the human stem cells to form new muscle fibers. When they blocked the activation of NF kappa B, which is activated by cellular damage and stress, the arsenic-exposed muscle recovered normally, suggesting that NF kappa B may play an important role in arsenic’s negative effects on muscle regeneration.
Citation: Zhang C, Ferrari R, Beezhold K, Stearns-Reider K, D'Amore A, Haschak M, Stolz D, Robbins PD, Barchowsky A, Ambrosio F. 2015. Arsenic promotes NF-κB-mediated fibroblast dysfunction and matrix remodeling to impair muscle stem cell function. Stem Cells; doi:10.1002/stem.2232. [Online 5 November 2015]