Hpgh

Hpgh is a human gene that encodes the enzyme hydroxyprostaglandin dehydrogenase (15‑hydroxyprostaglandin dehydrogenase), a key regulator of prostaglandin metabolism. The gene is located on chromosome 4q13.2 and comprises seven exons spanning approximately 3.4 kb of DNA. Transcription of Hpgh produces multiple splice variants, the most common of which yields a 349‑amino‑acid protein that is highly conserved across mammalian species.

Functionally, Hpgh‐encoded 15‑hydroxyprostaglandin dehydrogenase catalyzes the oxidation of the 15‑hydroxy group of prostaglandin E2 (PGE2) and other prostaglandins, converting them into inactive 15-keto metabolites. By controlling the intracellular concentration of active prostaglandins, the enzyme modulates inflammatory responses, pain perception, and vascular tone. The protein is predominantly expressed in liver, kidney, and colon, but its expression is also detectable in various tissues including the skin, heart, and brain.

Clinical relevance has been observed in several contexts. Reduced expression or activity of Hpgh can lead to prolonged PGE2 signaling, contributing to the development of chronic inflammation, gastric ulceration, and certain cancers such as colon, breast, and prostate malignancies. Conversely, overexpression of Hpgh has been associated with the suppression of tumor growth in preclinical models, likely due to dampening of prostaglandin‑mediated proliferation signals. Genetic polymorphisms within the Hpgh locus have been investigated as potential risk factors for inflammatory bowel disease and other autoimmune conditions, though results remain inconclusive.

Therapeutic strategies aimed at modulating Hpgh activity are under investigation. Small‑molecule activators of 15‑hydroxyprostaglandin dehydrogenase are being explored as potential anti‑inflammatory agents, while inhibitors are considered for conditions where elevated prostaglandin clearance might be beneficial. Current research continues to elucidate the full spectrum of Hpgh’s biological roles and its implications for human health.