Kentucky: 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.
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.
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
"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."
study was conducted jointly between Tai and investigators from Case
Western Reserve University in Cleveland and the University of Texas
Southwestern Medical Center in Dallas.