Estradiol differentially regulates DUX4, ?-catenin and PAX3/PAX7 in primary myoblasts of facioscapulohumeral muscular dystrophy patients

Abstract

Objectives: There is a clinical variability and heterogeneity among Facioscapulohumeral Muscular Dystrophy (FSHD) patients. Escalation after menopause in women, early onset in men suggests that estrogen might be a protective factor on the course of FSHD. In spite of few molecular studies supporting the protective role of estrogen in FSHD in vitro, there is no study revealing the effect of estradiol on the protein levels of DUX4, β-catenin and PAX3/PAX7. In present study, we investigated the effect of estradiol treatment on the expressions of DUX4, β-catenin and PAX3/PAX7 protein levels. Materials and Methods: Primary myoblasts of 63 and 71 years old (63yM/71yM) males; 47 years old (47yF) female FSHD patients were used. Cells were processed under these conditions; (i) untreated, (ii) 10 nM-30 min estradiol and (iii) 10 nM-4 h estradiol treated. The expression of DUX4, PAX3/ PAX7 and β-catenin were examined by western-blotting. Results: Expression of DUX4 significantly downregulated after 4 h treatment of estradiol while PAX3/PAX7 56 kDa variant expression upregulated in 71yM cells. β-catenin and PAX3 expression was variable among the samples. Conclusion: Our results suggest that estrogen might be a palliative treatment option via downregulation of DUX4 protein in DUX4 expressing FSHD patients. Keywords: β-catenin; DUX4; estradiol; facioscapulohumeral muscular dystrophy; FSHD; PAX3; PAX7; skeletal muscle.