SMAD3 and systemic sclerosis: ENG plays an essential role in the fibrotic process of systemic sclerosis (SSc) by promoting the TGF-β signaling pathway through phosphorylation of proteins such as mothers against decapentaplegic homolog 1 (SMAD1) and mothers against decapentaplegic homolog 3 (SMAD3), as well as by inducing the production of ECM-associated proteins such as collagen and connective tissue growth factor (CCN2) [24].