Increased expression of TLR4 and GSDMD has been observed in both patients with DN and corresponding animal models, and suppressing the TLR4/NF-κB signaling cascade reduces the expressions of caspase-1 and GSDMD, indicating its involvement in GSDMD-associated pyroptosis in DN.475,476 Moreover, TLR4 can exacerbate DN tubular injury and fibrosis through the canonical pyroptosis pathway. This evidence concerns the gene NFKB1 and liver dysplastic nodule.