[PGD(2)/L-PGDS system in hypertension and renal injury].
Prostaglandin D(2) (PGD(2)) and its metabolites bind to the intracellular PPARs to regulate vasoactive substances involved in vascular remodeling through regulation of mRNAs transcription as well as through receptor-mediated mechanisms. PGD(2) decreases inducible NO, PAI-1, endothelin, and VCAM expression through inhibition to NF kappa B, STAT, or AP-1 transcription factors, which are regulated by cytokines/immune system. Moreover, transfer of L-PGDS (PGD(2) synthase) into the intracellular space of EC or SMC increases intracellular PGD(2), thereby decreasing these substances. PGD(2) attenuates in vivo organ injury mediated by cytokines and the immune system. The pretreatment with PGD(2) attenuates the liver damage and hemodynamic collapse following LPS. Dahl salt-sensitive rats, with decreased PGD(2) in the outer medulla of the kidney, are prone to hypertensive kidney injury. Serum L-PGDS level is increased in renal dysfunction through a decrease in glomerular filtration. L-PGDS in urine may be derived from a failure of tubular reabsorption or from in situ synthesis. Urinary L-PGDS excretion markedly increases in the early stage of kidney injury, and urinary L-PGDS is a useful predictor of the forthcoming renal injury. Indeed, urinary L-PGDS precedes clinically overt proteinuria or other parameters indicating renal dysfunction in hypertension, primary renal diseases, and diabetes in humans. PGD(2)/L-PGDS system is a Cinderella of vascular biology.
Uehara
Yoshio
Y
Health Service Center University of Tokyo, Bunkyo, Japan. uehara-2im@h.u-tokyo.ac.jp
D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D019746:Intramolecular Oxidoreductases / Q000502:physiology*; D007674:Kidney Diseases / Q000503:physiopathology*; D054834:Lipocalins; D015230:Prostaglandin D2 / Q000502:physiology*; D051381:Rats
D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2