TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.

Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD
Science. 2015 348 (6240): aaa2340

PMID: 26068857 · PMCID: PMC4481126 · DOI:10.1126/science.aaa2340

Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.

Copyright © 2015, American Association for the Advancement of Science.

MeSH Terms (14)

Animals Bone Marrow Transplantation Colitis Dinoprostone Enzyme Inhibitors Hematopoiesis Hydroxyprostaglandin Dehydrogenases Liver Regeneration Mice Mice, Knockout Prostaglandins Pyridines Regeneration Thiophenes

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