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

• Published in: International immunopharmacology 2021-12, Vol.101 (Pt B), p.108176-108176, Article 108176
• Main Authors: Sun, Chen-Chen, Zhou, Zuo-qiong, Yang, Dong, Chen, Zhang-lin, Zhou, Yun-yi, Wen, Wei, Feng, Chen, Zheng, Lan, Peng, Xi-Yang, Tang, Chang-Fa
• Format: Article
• Language: English
• Subjects: 15-Hydroxyprostaglandin dehydrogenase (NAD+); 15-PGDH; Aging; Biological activity; Biomedical materials; Bone marrow; Breast cancer; Cancer; Cell differentiation; Cell proliferation; Damage prevention; Degradation; Degrades; Enzymes; Heredity; Mammals; Mutation; Organic anion transporting polypeptide; Osteoarthropathy; Oxidation; Pathology; Physiology; Prostaglandin; Prostaglandin E2; Prostaglandins; Protein transport; Regeneration; Therapeutic targets; Tissue engineering; Tissues; Tumor suppressor genes; Tumors
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108176

•15-PGDH degrades PGs to attenuate PG-mediated signaling and activity.•15-PGDH suppresses tumor progression and development through its targeting of PGs.•15-PGDG is a marker and potential therapeutic target for aging-associated diseases. 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.