15-hydroxyprostaglandin dehydrogenase (NAD+) (15-PGDH)

15-hydroxyprostaglandin dehydrogenase (NAD+), frequently abbreviated as 15-PGDH, is the key enzyme involved in the catabolism of prostaglandins and other eicosanoids (UniProt P15428). It catalyzes the conversion of the 15-hydroxyl group of prostaglandins, such as PGE2, PGF2alpha, and PGD2, into a 15-keto group, effectively neutralizing their biological signaling capabilities. Because PGE2 is a potent mediator of tissue repair and stem cell fitness, 15-PGDH acts as a metabolic brake on regenerative processes (Zhang et al., Science, 2015). In the context of oncology, 15-PGDH is widely recognized as a tumor suppressor, as its loss leads to elevated PGE2 levels that can drive chronic inflammation and tumor growth (Tai et al., Carcinogenesis, 2007). Conversely, pharmacological inhibition of 15-PGDH is being explored as a pro-regenerative therapy to accelerate recovery from bone marrow transplants, treat inflammatory bowel disease, and promote wound healing. Small molecule inhibitors like SW033291 have demonstrated the ability to double tissue PGE2 levels and significantly enhance the regenerative capacity of various organs in preclinical models (Desai et al., Science, 2018).

Other names

HPGDPGDH115-PGDHProstaglandin dehydrogenase 1Eicosanoid oxidoreductaseNAD+-dependent 15-hydroxyprostaglandin dehydrogenase

Inhibition of 15-PGDH prevents the degradation of Prostaglandin E2 (PGE2), leading to increased local concentrations of PGE2 which activates EP receptors to promote tissue repair and stem cell proliferation.