Recent advances in studies of 15-PGDH as a key enzyme for the degradation of prostaglandins

Int Immunopharmacol. 2021 Dec;101(Pt B):108176. doi: 10.1016/j.intimp.2021.108176. Epub 2021 Oct 13.

Abstract

15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) is ubiquitously expressed in mammalian tissues and catalyzes the degradation of prostaglandins (PGs; mainly PGE2, PGD2, and PGF2α) in a process mediated by solute carrier organic anion transport protein family member 2A1 (SLCO2A1; also known as PGT, OATP2A1, PHOAR2, or SLC21A2). As a key enzyme, 15-PGDH catalyzes the rapid oxidation of 15-hydroxy-PGs into 15-keto-PGs with lower biological activity. Increasing evidence suggests that 15-PGDH plays a key role in many physiological and pathological processes in mammals and is considered a potential pharmacological target for preventing organ damage, promoting bone marrow graft recovery, and enhancing tissue regeneration. Additionally, results of whole-exome analyses suggest that recessive inheritance of an HPGD mutation is associated with idiopathic hypertrophic osteoarthropathy. Interestingly, as a tumor suppressor, 15-PGDH inhibits proliferation and induces the differentiation of cancer cells (including those associated with colorectal, lung, and breast cancers). Furthermore, a recent study identified 15-PGDH as a marker of aging tissue and a potential novel therapeutic target for resisting the complex pathology of aging-associated diseases. Here, we review and summarise recent information on the molecular functions of 15-PGDH and discuss its pathophysiological implications.

Keywords: 15-PGDH; Degrades; Pathology; Physiology; Prostaglandin.

Publication types

  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Biomarkers / metabolism
  • Hydroxyprostaglandin Dehydrogenases / antagonists & inhibitors*
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxyprostaglandin Dehydrogenases / metabolism*
  • Prostaglandins / metabolism*

Substances

  • Biomarkers
  • Prostaglandins
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase