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

15-hydroxyprostaglandin dehydrogenase [NAD(+)] is an NAD+-dependent oxidoreductase enzyme encoded by the HPGD gene. It catalyzes the oxidation of the C15(S)-hydroxyl group on various bioactive lipids—primarily eicosanoids such as prostaglandins—converting them into their corresponding inactive keto-metabolites. This reaction represents the first step in the metabolic/catabolic pathway responsible for terminating signaling by these potent lipid mediators. By regulating local concentrations of molecules like PGE₂—which are involved in inflammation, cell proliferation/survival/apoptosis decisions, vascular tone regulation, reproduction/fertility maintenance—the enzyme plays critical roles across diverse physiological systems including immunity and pregnancy maintenance. Loss-of-function mutations or downregulation are associated with increased risk/progression/severity across several cancer types due to unchecked pro-tumorigenic signaling from accumulated active prostanoids; conversely pharmacologic inhibition has shown promise for stimulating tissue repair/regeneration after injury but carries theoretical risks related to tumor promotion if not carefully controlled.

Other names

15-PGDHHPGDHydroxyprostaglandin dehydrogenase 15-(NAD)Prostaglandin E2 9-reductase (less common)EC 1.1.1.141

For inhibitors such as SW033291 or other small molecules targeting this enzyme: - Inhibition of enzymatic activity leads to increased local concentrations of active prostaglandins like PGE2. - This can promote tissue regeneration or modulate inflammatory responses depending on context. For DMARDs that upregulate expression: - Indirect increase in HPGD protein reduces PGE2 levels by enhancing its catabolism.