Publication Date:
2015-06-13
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- 1P01CA95471-09/CA/NCI NIH HHS/ -- 5P30 CA142543-03/CA/NCI NIH HHS/ -- P01 CA095471/CA/NCI NIH HHS/ -- P30 CA043703/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK097948/DK/NIDDK NIH HHS/ -- P50 CA130810/CA/NCI NIH HHS/ -- P50 CA150964/CA/NCI NIH HHS/ -- R01 CA127590/CA/NCI NIH HHS/ -- R25 CA148052/CA/NCI NIH HHS/ -- R25CA148052/CA/NCI NIH HHS/ -- U54 HL119810/HL/NHLBI NIH HHS/ -- U54HL119810/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea. ; 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. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; 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. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. ; 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. ; Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA. ; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. ; Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. ; College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. ; 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. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; 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. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068857" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bone Marrow Transplantation
;
Colitis/enzymology/prevention & control
;
Dinoprostone/metabolism
;
Enzyme Inhibitors/chemistry/pharmacology
;
Hematopoiesis/drug effects
;
Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/genetics/*physiology
;
Liver Regeneration/drug effects
;
Mice
;
Mice, Knockout
;
Prostaglandins/*metabolism
;
Pyridines/chemistry/pharmacology
;
Regeneration/drug effects/genetics/*physiology
;
Thiophenes/chemistry/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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