Inflammation and  microRNA connection to muscular dystrophy

Inflammation and  microRNA connection to muscular dystrophy

Patients with Becker and Duchenne muscular dystrophy express variable amounts of dystrophin protein. The molecular basis for this variability is not known.

Scientists show that in muscle from Becker patients dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31).  microRNAs are expressed in dystrophic myofibers and increase with age and disease severity.

In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue.TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy.

These findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.