TGF Beta
Inhibition of TGF-beta.
Andrew Hoey of the University of Southern Queensland in Australia explained the role of fibrosis and what possibly could be done to prevent or to reduce it. Fibrosis, or scar tissue, is caused by the excessive production of connective tissue and its deposition between the skeletal and cardiac muscle fibers replacing degraded and lost fibers. Under normal circumstances, connective tissue holds the muscle fibers together, but increased levels lead to muscle stiffness and contractures. Connective tissue consists mainly of the protein collagen, a rather inelastic molecule that is generated from cells, called fibroblasts. This occurs during the degeneration and regeneration process in Duchenne Muscular dystrophy under the influence of growth factors, among them transforming growth factor beta, TGF-beta.
TGF-beta promotes the synthesis and merger of different collagen molecules to produce the highly inflexible connective tissue. Thus inhibiting the activity of TGF-beta may be a possible mechanism to reduce fibrosis. One such drug that may have potential is pirfenidone which is an approved medication for treatment of fibrosis in the lungs. Eight month old mdx mice were administered this drug and after seven months of treatment showed reduced levels of TGF-beta and restored heart function almost to normal, but fibrosis was not reduced in these old mdx mice. The possibility of the drug being more effective in younger mice will be examined in future experiments.
From Günter Scheuerbrandt Report of the PPMD Conference 2006