
A study published online on January 2 in the Journal of Cell Biology describes how increased production of a microRNA promotes progressive muscle deterioration in a mouse model of Duchenne muscular dystrophy (DMD).
As DMD patients age, their damaged muscle cells are gradually replaced by collagen-rich, fibrous tissue. This muscle fibrosis is partly induced by the growth factor TGF-beta, which is highly activated in DMD patients, though exactly how this cytokine promotes fibrogenesis is unclear. Pura Muñoz-Cánoves and colleagues examined the role of miR-21, a microRNA whose production is stimulated by TGF-beta signaling.
miR-21 was upregulated in the collagen-producing fibroblasts of both DMD patients and mice that develop disease symptoms similar to human muscular dystrophy (so-called mdx mice). Inhibiting miR-21 reduced collagen levels and prevented, or even reversed, fibrogenesis in diseased animals, whereas mdx mice overexpressing the microRNA produced more collagen and developed fibrotic muscles at earlier ages.
TGF-beta inhibitors prevent muscle fibrosis but have damaging side effects; this study suggests that uPA or miR-21 may make attractive alternative drug targets. Muñoz-Cánoves now wants to investigate the function of miR-21 in other cell types that influence muscle homeostasis, such as the macrophages involved in tissue repair.
Source: Eurekalert
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