We demonstrated evidence that loss of Chop represses Hmgb1/TLR4 signaling following UUO induction, leading to repressed NFκB transcriptional activity along with suppressed IL-1β production, which then reduces TGF-β1 production and Pi3K/Akt activity to attenuate the development of renal fibrosis. Here, TGFB1 is linked to renal fibrosis.