Animal and clinical studies have reported the roles for PI3K/Akt/mTOR and TGF-β1/Smad2 signaling pathways in the early stage of DN, and the blockade of these pathways slows the progression and development of DN (Gangadharan-Komala et al., 2016; Li et al., 2016). Here, SMAD2 is linked to liver dysplastic nodule.