Fibronectin-EDA and tenascin-C may activate Toll receptor 4 (TLR4) and lead to uncontrolled extracellular matrix (ECM) deposition in systemic sclerosis (SSc), which subsequently enhances transforming growth factor beta (TGF-β) signaling, thus promoting fibrotic responses. Here, TGFB1 is linked to systemic sclerosis.