Ceramide kinase contributes to proliferation but not to prostaglandin E2 formation in renal mesangial cells and fibroblasts.

摘要: Background/Aims: Ceramide kinase (CerK) catalyzes the generation of sphingolipid ceramide-1-phosphate (C1P) which regulates various cellular functions including cell growth and death, inflammation. Here, we used a novel catalytic inhibitor CerK, NVP-231, CerK knockout cells to investigate contribution proliferation inflammation in renal mesangial fibroblasts. Methods: Cells were treated with NVP-231 [3H]-thymidine incorporation into DNA, [3H]-arachidonic acid release, prostaglandin E2 (PGE2) synthesis, cycle distribution, apoptosis determined. Results: Treatment rat mouse fibroblasts decreased DNA but not agonist-stimulated arachidonic release or PGE2 synthesis. Similarly, synthesis was reduced CERK The anti-proliferative effect on due M phase arrest as determined using mitosis markers phospho-histone H3, cdc2 polo-like kinase-1, induction apoptosis. Moreover, loss sensitized towards stress-induced Conclusions: Our data demonstrate that induces formation fibroblasts, suggest targeted inhibition has potential for treating mesangioproliferative kidney diseases.