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, Gretchen A. Larusch, Lucy He, Fabio Cominelli, Luca Di Martino, Zora Djuric, Ginger L. MilneMark 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

Research output: Contribution to journalArticle

85 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2340
JournalScience
Volume348
Issue number6240
DOIs
StatePublished - Jun 12 2015

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15-hydroxyprostaglandin dehydrogenase
Prostaglandins
Regeneration
Enzymes
Dinoprostone
Bone Marrow
Tissue Expansion
Hematopoietic System
Bone Marrow Transplantation
Knockout Mice
Colon
Stem Cells

ASJC Scopus subject areas

  • General

Cite this

Zhang, Y., Desai, A., Yang, S. Y., Bae, K. B., Antczak, M. I., Fink, S. P., ... Markowitz, S. D. (2015). Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science, 348(6240), [2340]. https://doi.org/10.1126/science.aaa2340

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

In: Science, Vol. 348, No. 6240, 2340, 12.06.2015.

Research output: Contribution to journalArticle

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, JKV & Markowitz, SD 2015, 'Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration', Science, vol. 348, no. 6240, 2340. https://doi.org/10.1126/science.aaa2340
Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP et al. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12;348(6240). 2340. https://doi.org/10.1126/science.aaa2340
Zhang, Yongyou ; Desai, Amar ; Yang, Sung Yeun ; Bae, Ki Beom ; Antczak, Monika I. ; Fink, Stephen P. ; Tiwari, Shruti ; Willis, Joseph E. ; Williams, Noelle S. ; Dawson, Dawn M. ; Wald, David ; Chen, Wei Dong ; Wang, Zhenghe ; Kasturi, Lakshmi ; Larusch, Gretchen A. ; He, Lucy ; Cominelli, Fabio ; Di Martino, Luca ; Djuric, Zora ; Milne, Ginger L. ; Chance, Mark ; Sanabria, Juan ; Dealwis, Chris ; Mikkola, Debra ; Naidoo, Jacinth ; Wei, Shuguang ; Tai, Hsin Hsiung ; Gerson, Stanton L. ; Ready, Joseph M. ; Posner, Bruce ; Willson, James K V ; Markowitz, Sanford D. / Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. In: Science. 2015 ; Vol. 348, No. 6240.
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AU - Wei, Shuguang

AU - Tai, Hsin Hsiung

AU - Gerson, Stanton L.

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