2. Academic Validation
  3. 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

  • Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.
Yongyou Zhang 1,  Amar Desai 1,  Sung Yeun Yang 2,  Ki Beom Bae 3,  Monika I Antczak 4,  Stephen P Fink 1,  Shruti Tiwari 5,  Joseph E Willis 6,  Noelle S Williams 4,  Dawn M Dawson 7,  David Wald 6,  Wei-Dong Chen 1,  Zhenghe Wang 8,  Lakshmi Kasturi 1,  Gretchen A Larusch 1,  Lucy He 1,  Fabio Cominelli 5,  Luca Di Martino 1,  Zora Djuric 9,  Ginger L Milne 10,  Mark Chance 11,  Juan Sanabria 12,  Chris Dealwis 13,  Debra Mikkola 1,  Jacinth Naidoo 4,  Shuguang Wei 4,  Hsin-Hsiung Tai 14,  Stanton L Gerson 15,  Joseph M Ready 16,  Bruce Posner 16,  James K V Willson 17,  Sanford D Markowitz 15
Affiliations

Affiliations

  • 1 Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 2 Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea.
  • 3 Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Surgery, Busan Paik Hospital, and Paik Institute of Clinical Research and Ocular Neovascular Research Center, Inje University, Busan, South Korea.
  • 4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5 Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
  • 6 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
  • 7 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 8 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 9 Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA.
  • 10 Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
  • 11 Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 12 Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
  • 13 Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 14 College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
  • 15 Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. [email protected] [email protected] [email protected] [email protected] [email protected].
  • 16 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. [email protected] [email protected] [email protected] [email protected] [email protected].
  • 17 Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. [email protected] [email protected] [email protected] [email protected] [email protected].
PMID: 26068857 DOI: 10.1126/science.aaa2340
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16968
    99.74%, 15-PGDH Inhibitor