15-hydroxyprostaglandin dehydrogenase [NAD+] (HPGD)

15-hydroxyprostaglandin dehydrogenase (HPGD), commonly referred to as 15-PGDH, is the primary enzyme responsible for the metabolic inactivation of prostaglandins, most notably prostaglandin E2 (PGE2) (UniProt P15428). It catalyzes the oxidation of the 15-hydroxyl group of prostaglandins to a 15-keto group, which significantly reduces their biological activity and terminates their signaling (PubMed: 25838370). HPGD is widely recognized as a tumor suppressor in various malignancies, including colon, lung, and breast cancers, where its expression is frequently lost or downregulated, leading to elevated PGE2 levels that drive tumor progression (PubMed: 15150476). In the context of regenerative medicine, HPGD has emerged as a major therapeutic target; its pharmacological inhibition leads to increased local PGE2 levels, which has been shown to accelerate the recovery of bone marrow, liver, and colon tissues following injury (Science, 2015, 348(6240)). Small molecule inhibitors like SW033291 are currently being investigated for their potential to enhance tissue healing and hematopoietic recovery in clinical settings (PubChem CID 71748056). Conversely, germline mutations in the HPGD gene are associated with primary hypertrophic osteoarthropathy, a condition characterized by digital clubbing and periostosis due to chronically elevated prostaglandin levels (PubMed: 18469813).

Other names

15-PGDHPGDHPGDH1SDR36C1Prostaglandin dehydrogenase 115-hydroxyprostaglandin dehydrogenase

Inhibition of HPGD prevents the metabolic degradation of prostaglandin E2 (PGE2), thereby increasing local PGE2 concentrations to promote tissue repair, stem cell fitness, and hematopoietic recovery.