Tim-3 mediated the activation of NF-κB induced by TNF-α.227 TNF receptor-1 inhibitor, R-7050 reduced renal damage and fibrosis in wild-type mice and mice with Krüppel-like factor 4 (KLF4)-deficient macrophages.210 Another TNF superfamily (TNFSF) member, TWEAK was proved to worsen the phenotype of ADPKD mice and renal fibrosis of UUO mice by activating NF-κB signaling.228,229 TWEAK is also an activator of nonclassical NF-κB signaling, and is the only cytokine demonstrated to activate nonclassical NF-κB signaling in tubules currently. The gene discussed is TNFSF12; the disease is renal fibrosis.