Wang et al. (2016) showed that TGR5 was upregulated in kidney specimens from DN patients and could be associated with DN progression. TGR5 agonist INT-777 alleviated DN by preventing renal oxidative stress and lipid accumulation in diabetic db/db mice. Similarly, another study showed that TGR5 activation ameliorated DN potentially by inhibiting the sphingosine 1-phosphate/sphingosine 1-phosphate receptor 2 signaling, reducing intercellular adhesion molecule-1, and then the expressions of transforming growth factorbeta1 and fibronectin (Yang et al., 2016). This evidence concerns the gene S1PR2 and liver dysplastic nodule.