In renal fibrosis, the loss of Chop gene represses Hmgb1/TLR4 signal pathway, leading to repressed NF-κB transcriptional activity along with suppressed IL-1β production, and reduced TGF-β1 production and PI3K/Akt activity to attenuate the development of fibrosis [26]. Here, TLR4 is linked to renal fibrosis.