TIMP1 and renal fibrosis: Smad3 can directly bind to the promoter region of the collagen gene to trigger collagen production, induce TIMP-1 to reduce the activity of MMP-1 in fibroblasts, inhibit the degradation of ECM, and promote fibrosis due to various causes [46–48], while some studies have shown that the role of smad2 in renal fibrosis is the opposite of that of smad3 [49–51].