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Tissue Regeneration. Inhibition of the Prostaglandin-Degrading Enzyme 15-PGDH Potentiates Tissue Regeneration

Tissue Regeneration. Inhibition of the Prostaglandin-Degrading Enzyme 15-PGDH Potentiates Tissue Regeneration

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, etc.

Science. 2015 Jun 12;348(6240):aaa2340.

PMID: 26068857

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP459147398	SW033291		459147-39-8	Price

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