Aim To study if inhibition of glutaminase has effect on polycystic kidney disease （PKD）development and to further investigate the mechanism for the effect. Methods Human autosomal dominant PKD epithelial cells were ...Aim To study if inhibition of glutaminase has effect on polycystic kidney disease （PKD）development and to further investigate the mechanism for the effect. Methods Human autosomal dominant PKD epithelial cells were used to form cysts which were treated with glutaminase specific inhibitors BPTES or CB839. The number and size of cysts were recorded. PKD mice were gavaged with CB839 for two weeks. Kidney morphology and renal func- tion were analyzed. Western blot and seahorse were used to investigate the mechanism. Results Glutaminase in- hibitor retarded the cysts development both in vitro and in vivo. The expression of glutaminase was higher in PKD mice compared to control mice. CB839 inhibited PKD development through reduction of mitrochondrial ATP pro- duction, then resulting into inhibiting proliferation and increasing apoptosis in abnormal renal epithelial cells which would form cysts. Conclusion Glutaminase inhibitor ameliorated the development of PKD. Glutaminase inhibitor might be developed as a candidate drug for PKD and can be combined with other drugs.展开更多
文摘Aim To study if inhibition of glutaminase has effect on polycystic kidney disease （PKD）development and to further investigate the mechanism for the effect. Methods Human autosomal dominant PKD epithelial cells were used to form cysts which were treated with glutaminase specific inhibitors BPTES or CB839. The number and size of cysts were recorded. PKD mice were gavaged with CB839 for two weeks. Kidney morphology and renal func- tion were analyzed. Western blot and seahorse were used to investigate the mechanism. Results Glutaminase in- hibitor retarded the cysts development both in vitro and in vivo. The expression of glutaminase was higher in PKD mice compared to control mice. CB839 inhibited PKD development through reduction of mitrochondrial ATP pro- duction, then resulting into inhibiting proliferation and increasing apoptosis in abnormal renal epithelial cells which would form cysts. Conclusion Glutaminase inhibitor ameliorated the development of PKD. Glutaminase inhibitor might be developed as a candidate drug for PKD and can be combined with other drugs.
