Duchenne muscular dystrophy of muscle fibrosis

a brand new study in the Journal of cellular Biology describes how increased creation of the microRNA miR-21 leads to progressive muscle deterioration in the mouse model of Duchenne muscular dystrophy. Muscle from an aged muscular dystrophy model mouse (left) consists of large collagen deposits (red), but these are reduced when miR-21 is inhibited (right).Researchers describe how increased production of a microRNA promotes progressive muscle deterioration in a mouse style of Duchenne muscular dystrophy (DMD), based on a study released on the web on January 2 inside Journal of mobile Biology .

As DMD individuals age, their broken muscle cells are gradually changed by collagen-rich, fibrous tissue. This muscle fibrosis is partly induced through the growth factor TGF-beta, which can be very activated in DMD patients, even though precisely how this cytokine promotes fibrogenesis is unclear. Pura Muñoz-Cánoves and colleagues examined the function of miR-21, a microRNA whose production is stimulated by TGF-beta signaling.

miR-21 was upregulated inside collagen-producing fibroblasts of equally DMD individuals and mice that produce illness symptoms comparable to person’s muscular dystrophy (so-called mdx mice). Inhibiting miR-21 lowered collagen levels and prevented, or even reversed, fibrogenesis in diseased animals, whereas mdx mice overexpressing the microRNA created more collagen and originated fibrotic muscles at earlier ages.

The research workers also discovered that TGF-beta activity and miR-21 production were regulated through the stability of two extracellular factors: uPA—a protease that activates TGF-beta—and its inhibitor PAI-1. mdx mice originated fibrotic muscles more swiftly inside absence of PAI-1, but these symptoms could quite possibly be reversed by inhibiting uPA with a medicine or quite possibly a specific siRNA. In add-on to producing more collagen, PAI-1–null fibroblasts also proliferated quickly considering the extra miR-21 induced by lively TGF-beta inhibited the tumor-suppressive phosphatase PTEN.

TGF-beta inhibitors prevent muscle fibrosis but have damaging side effects; this study suggests that uPA or miR-21 may make attractive option medicine targets. Muñoz-Cánoves now wishes to investigate the function of miR-21 in other mobile kinds that effect muscle homeostasis, for example the macrophages included in tissue repair.

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