SMAD4 and liver dysplastic nodule: 2019). Both TGF-β and HG could activate the TGF-β/Smads signal pathway and promote the excess expression of ECM, which was a hallmark of DN (Li J, Wu B et al. 2020). Smad2/3 and Smad4 are downstream factors of the TGF-β/Smads signal pathway, followed by the stimulation of HG or TGF-β, Smad4 will bind to the phosphorylated Smad2/3 to form a complex and then translocated to the nucleus as transcriptional factors to promote the expression of ECM and inhibition of TGF-β/Smads signal pathway could alleviate excess ECM expression and improve DN (Hu et al. 2021).