SMAD4 and liver dysplastic nodule: 2003; Meng et al. 2016; Chen et al. 2017). The downstream signalling molecules include Smad2, Smad3, Smad4 and Smad7. The TGF-β/Smads signalling pathway is activated both in the DN animal model and high glucose-induced diabetic cell model, and then facilitates p-Smad2, p-Smad3 and Smad4 to form a complex translocated to the nucleus as a transcriptional factor of ECM (Xin et al. 2013; Guan et al. 2018).