We speculated that it might be related to the fact that Smad 2 and Smad4 does not have DNA-binding domains, but acts as a regulator of Smad3-based gene transcription [29].Of course, due to the complexity of the mechanism of TGF-β1-induced renal fibrosis, our findings cannot yet determine whether TGF-β1-induced up-regulation of TRIM39 expression are related to non-Smad pathways, which may be further studied in the future. The gene discussed is SMAD3; the disease is renal fibrosis.