Characterization of Wilms' Tumour 1 (Wt1) as a Biomarker for Fibrosis in Duchenne Muscular Dystrophy
Abstract
Duchenne muscular dystrophy (DMD) is the most common inherited pediatric muscle dystrophy. It is characterized by muscle degeneration, resulting in fibrosis that is a significant impediment to both endogenous muscle repair and any potential regenerative strategy. At present, there are few therapies that specifically address fibrosis and microenvironment improvement, but one possibility rests in targeting the Wilms’ tumour 1 (Wt1) protein. Wt1 is a zinc finger transcription factor, recently shown to be expressed in fibrotic conditions such as Dupuytren’s disease and pulmonary fibrosis. This thesis examines the expression pattern of Wt1 in several mouse models of DMD, through both histological quantification of Wt1 protein, and quantification of Wt1 isoform mRNA. Additionally, fibrosis is quantified through Masson’s trichrome staining of collagen. An increased proportion of Wt1 immunoreactive nuclei was found in the diaphragm and gastrocnemius of DMD disease models prior to and during early fibrosis, but returned to basal levels during late fibrosis. These results suggest that nuclear Wt1 immunoreactivity may precede college deposition, and that it should be investigated further in the future.