However, in Pkd1RC/RC kidneys, nintedanib treatment did not change SMAD3 activity, an important component of TGFβ-signaling pathway and a contributor to renal fibrosis, as suggested by no change in pSMAD3/SMAD3 ratio, when compared with vehicle treatment (Supplemental 4A, B). The gene discussed is SMAD3; the disease is renal fibrosis.