In the canonic TGF-β pathway, once activated, TGF-β1 binds to its receptor II to activate the receptor I and the downstream regulatory Smad proteins (Smad2 and Smad3), facilitated by Co-Smad (Smad4), to translocate into the nucleus to initiate the target gene transcription and cause renal fibrosis, which is negatively regulated by Smad7 19,20. This evidence concerns the gene SMAD3 and renal fibrosis.