These results suggested that MIF-CD74 signaling should regulate renal fibrosis in ADPKD kidneys through promoting the expression of TGF-β and the activation of Smad3, and targeting MIF with ISO-1 ameliorated interstitial fibrosis by blocking TGF-β induced activation of SMAD3. The gene discussed is TGFB1; the disease is renal fibrosis.