Abnormal of STAT3 activation in chronic kidney disease may promote tubulointerstitial fibrosis mediated by tubular epithelial cells, potentially by upregulating the of aquaporin 2 (AQP2), lipocalin‐2 (Lcn‐2), and tissue inhibitor of metalloproteinase 1 (TIMP‐1) expression.[29, 30, 31] AQP2 protein expression and Lcn‐2 and TIMP‐1 transcriptional levels were signficantly increased in the kidneys of db/db mice. This evidence concerns the gene TIMP1 and chronic kidney disease.