Effect of 12-lipoxygenase on the AT1 receptor expression in mesangial cells / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effect of 12-lipoxygenase (12-LO) on the angiotensinⅡtype 1 receptor(ATlR) expression in mesangial cells (MC).Methods p38 MAPK activation and ECM protein expression were determined using AngⅡ-stimulated MC derived from normal and 12-LO knockout mice.AT1R expression was determined using 12-LO product 12(S)- HETE-stimulated MC,MC transfected with 12-LO gene and microdissected glomeruli derived from 12-LO knockout mice.RT-PCR and Western blot were used for evaluating mRNA and protein expression respectively.Results AngⅡstimulation increased p38 MAPK activation and ECM protein expression in normal MC,but not in MC derived from 12-LO knockout mice.Time-dependent and dose-dependent experiment showed that 12 (S)- HETE increased AT1R protein' expression in MC. Similarly,12 (S)-HETE increased AT1R mRNA expression in MC compared with control MC (P＜0.01). Furthermore,AT1R expression was lower in glomeruli derived from 12-LO knockout mice relative to genetic controls (P＜0.01) and MC stably overexpressing 12-LO had greater AT1R protein and mRNA expression relative to control MC (P＜0.01).Conclusion 12-LO activation can upregulate ATIR expression in MC.