Prostaglandin D Synthase
Prostaglandin D Synthase catalyzes PGH2 isomerization to PGD2, linking cyclooxygenase-derived prostanoid biosynthesis to sleep, pain, allergy, inflammation, and downstream PGJ2/PPARγ biology[1][2]. Mechanistically, PGD2 acts through DP and CRTH2 receptors, while PGDS enzymes connect arachidonic acid metabolism with central nervous system and immune-cell signaling[1][2]. In disease models, HPGDS augments inflammation followed by muscle injury, and HPGDS inhibition ameliorates muscular necrosis in mdx mice[3]. In Duchenne muscular dystrophy myocardium, HPGDS increases in mast cells and pericytes, supporting cell-type-focused PGD2 research in fibrotic cardiac specimens[4]. Compared with related isoforms, lipocalin-type PGDS and hematopoietic PGDS differ in amino acid sequence, tertiary structure, evolutionary origin, chromosomal and cellular localization, tissue distribution, and functional relevance[1]. Mouse knockout data further distinguish isoforms because L-Pgds deletion, but not H-Pgds deletion, elevates blood pressure and accelerates thrombogenesis[5]. For experimental applications, HQL-79 binds the human HPGDS catalytic cleft, while TAS-205 showed favorable safety in DMD patients and requires further efficacy evaluation[6][7].
References:
- [1]. Urade Y, et al. Lipocalin-type and hematopoietic prostaglandin D synthases as a novel example of functional convergence. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:375-82. [Content Brief]
- [2]. Smith WL, et al. Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem Rev. 2011 Oct 12;111(10):5821-65. [Content Brief]
- [3]. Mohri I, et al. Inhibition of prostaglandin D synthase suppresses muscular necrosis. Am J Pathol. 2009 May;174(5):1735-44. [Content Brief]
- [4]. Hamamura K, et al. Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy. Int J Mol Sci. 2024 Feb 3;25(3):1846. [Content Brief]
- [5]. Song WL, et al. Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice. J Pharmacol Exp Ther. 2018 Dec;367(3):425-432. [Content Brief]
- [6]. Aritake K, et al. Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase. J Biol Chem. 2006 Jun 2;281(22):15277-86. [Content Brief]
- [7]. Komaki H, et al. Early phase 2 trial of TAS-205 in patients with Duchenne muscular dystrophy. Ann Clin Transl Neurol. 2020 Feb;7(2):181-190. [Content Brief]
