Key prostaglandin metabolic enzyme shows promise as drug target for tissue regeneration

A new study co-led by Hsin-Hsiung Tai, professor of pharmaceutical sciences at the University of Kentucky, suggests that a key prostaglandin (PG) metabolic enzyme shows promise as a drug target to help tissue regeneration and repair, particularly after bone marrow transplantation and tissue injuries.

Published in the June 12 issue of Science, the study looked at the role of 15-PGDH, an enzyme that quickly degrades a bioactive lipid called PGE2, in tissue regeneration in mouse models. Recent studies have shown that PGE2 may have a positive effect on tissue regeneration. However, 15-PGDH negatively regulates tissue regeneration and repair as it negates the lipid's ability to stimulate tissue regeneration.

The investigators discovered a tight binding inhibitor known as SW033291 which showed promise to inhibit 15-PGDH, allowing PGE2 levels to increase in the bone marrow, colon, lung and liver of the normal mice as much as that found in those of the 15-PGDH knockout mice.

Mice treated with SW033291 showed a six-day faster reconstitution of hematopoiesis after bone marrow transplantation, with accelerated recovery of their blood cells counts than the control group. The treated mice also showed a marked resistance to experimentally induced colitis, in addition to enhanced liver regeneration following partial hepatectomy.

"This is the first report describing the discovery of a potent and specific inhibitor of 15-PGDH, which had a significant positive affect on hematopoiesis and tissue regeneration," Tai said. "This enzyme may prove to be a promising target for relevant drug development and these drugs could have applications for patients undergoing bone marrow transplantation, surgical resection of certain liver or colon cancers, and the treatment of ulcerative colitis."