SMAD3 and renal fibrosis: 3,4 Renal fibrosis is associated with the activation of fibroblasts, which differentiate into myofibroblasts, causing changes in cell morphology and increased production of fibrosis markers such as alpha-smooth muscle actin (α-SMA) and collagen. This process is regulated by several signaling pathways, including the transforming growth factor beta (TGF-β)/Smad3 signaling pathway. 3-5 TGF-β1 can also promote the differentiation of fibroblasts and macrophages into myofibroblasts, worsening renal fibrosis. 4, 5