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

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.

Citation

Yongyou Zhang, Amar Desai, Sung Yeun Yang, Ki Beom Bae, Monika I Antczak, Stephen P Fink, Shruti Tiwari, Joseph E Willis, Noelle S Williams, Dawn M Dawson, David Wald, Wei-Dong Chen, Zhenghe Wang, Lakshmi Kasturi, Gretchen A Larusch, Lucy He, Fabio Cominelli, Luca Di Martino, Zora Djuric, Ginger L Milne, Mark Chance, Juan Sanabria, Chris Dealwis, Debra Mikkola, Jacinth Naidoo, Shuguang Wei, Hsin-Hsiung Tai, Stanton L Gerson, Joseph M Ready, Bruce Posner, James K V Willson, Sanford D Markowitz. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science (New York, N.Y.). 2015 Jun 12;348(6240):aaa2340

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PMID: 26068857

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