SMAD3 and renal fibrosis: As such, TGF-β1/Smad3 signaling may induce Erbb4-IR to further increase its fibrotic response by inhibiting the Smad7-dependent negative feedback loop, and the kidney-specific silencing of Erbb4-IR accordingly upregulated renal Smad 7, thus blocking TGF-β1/Smad3-mediated renal fibrosis in vivo and in vitro.