PPAR γ agonist rosiglitazone suppresses renal mPGES-1/PGE2 pathway in db/db mice

Evidence had shown the detrimental effect of prostaglandin (pg) e2 in diabetic nephropathy (dn) of stz-induced type-1 diabetes but its role in the development of dn of type-2 diabetes remains uncertain. the present study was undertaken to investigate the regulation of pge2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (ppar)γ and pge2 synthesis in the kidneys of db/db mice. strikingly,urinary pge2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of cox-2 and mpges-1. in contrast,the protein expressions of cox-1,mpges-2,cpges,and 15-hydroxyprostaglandin dehydrogenase (15-pgdh) were not altered. following 1-week rosiglitazone (rosi) therapy,urinary pge2,but not other prostanoids,was reduced by 57% in parallel with significant reduction of mpges-1 protein and ep4 mrna expressions. by immunohistochemistry,mpges-1 was significantly induced in the glomeruli of db/db mice,which was almost entirely abolished by rosi. in line with the reduction of glomerular mpges-1,the glomerular injury score showed a tendency of improvement after 1 week of rosi therapy. collectively,the present study demonstrated an inhibitory effect of pparγ activation on renal mpges-1/pge2/ep4 pathway in type-2 diabetes and suggested that mpges-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated dn. © 2013 ying sun et al.