Moreover, forced expression of GPR65, pH 6.6 and BTB09089 significantly promoted, while knockout of Gpr65, pH 8.2 and ZINC62678696 reduced the phosphorylation of IKK, IĸBα, NF-ĸB p65, MLK3, MKK7 and JNK in HMs and RAW264.7 cells (Fig. 6b; Additional file 1: Fig. S21b), suggesting that silencing GPR65 alleviated hepatic fibrosis and M1 macrophage polarization mainly through the JNK and NF-κB pathways. The gene discussed is NFKB1; the disease is Hepatic fibrosis.