| Literature DB >> 26068857 |
Yongyou Zhang1, Amar Desai1, Sung Yeun Yang2, Ki Beom Bae3, Monika I Antczak4, Stephen P Fink1, Shruti Tiwari5, Joseph E Willis6, Noelle S Williams4, Dawn M Dawson7, David Wald6, Wei-Dong Chen1, Zhenghe Wang8, Lakshmi Kasturi1, Gretchen A Larusch1, Lucy He1, Fabio Cominelli5, Luca Di Martino1, Zora Djuric9, Ginger L Milne10, Mark Chance11, Juan Sanabria12, Chris Dealwis13, Debra Mikkola1, Jacinth Naidoo4, Shuguang Wei4, Hsin-Hsiung Tai14, Stanton L Gerson15, Joseph M Ready16, Bruce Posner16, James K V Willson17, Sanford D Markowitz15.
Abstract
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.Entities:
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Year: 2015 PMID： 26068857 PMCID： PMC4481126 DOI： 10.1126/science.aaa2340
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728