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15-PGDH regulates hematopoietic and gastrointestinal fitness during aging

Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cells’ regenerative capacity, we tested the hypothesis that the prostaglandi...

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Autores principales: Ho, Won Jin, Smith, Julianne N. P., Park, Young Soo, Hadiono, Matthew, Christo, Kelsey, Jogasuria, Alvin, Zhang, Yongyou, Broncano, Alyssia V., Kasturi, Lakshmi, Dawson, Dawn M., Gerson, Stanton L., Markowitz, Sanford D., Desai, Amar B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119474/
https://www.ncbi.nlm.nih.gov/pubmed/35587945
http://dx.doi.org/10.1371/journal.pone.0268787
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author Ho, Won Jin
Smith, Julianne N. P.
Park, Young Soo
Hadiono, Matthew
Christo, Kelsey
Jogasuria, Alvin
Zhang, Yongyou
Broncano, Alyssia V.
Kasturi, Lakshmi
Dawson, Dawn M.
Gerson, Stanton L.
Markowitz, Sanford D.
Desai, Amar B.
author_facet Ho, Won Jin
Smith, Julianne N. P.
Park, Young Soo
Hadiono, Matthew
Christo, Kelsey
Jogasuria, Alvin
Zhang, Yongyou
Broncano, Alyssia V.
Kasturi, Lakshmi
Dawson, Dawn M.
Gerson, Stanton L.
Markowitz, Sanford D.
Desai, Amar B.
author_sort Ho, Won Jin
collection PubMed
description Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cells’ regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss of Hpgd expression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness.
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spelling pubmed-91194742022-05-20 15-PGDH regulates hematopoietic and gastrointestinal fitness during aging Ho, Won Jin Smith, Julianne N. P. Park, Young Soo Hadiono, Matthew Christo, Kelsey Jogasuria, Alvin Zhang, Yongyou Broncano, Alyssia V. Kasturi, Lakshmi Dawson, Dawn M. Gerson, Stanton L. Markowitz, Sanford D. Desai, Amar B. PLoS One Research Article Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cells’ regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss of Hpgd expression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness. Public Library of Science 2022-05-19 /pmc/articles/PMC9119474/ /pubmed/35587945 http://dx.doi.org/10.1371/journal.pone.0268787 Text en © 2022 Ho et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ho, Won Jin
Smith, Julianne N. P.
Park, Young Soo
Hadiono, Matthew
Christo, Kelsey
Jogasuria, Alvin
Zhang, Yongyou
Broncano, Alyssia V.
Kasturi, Lakshmi
Dawson, Dawn M.
Gerson, Stanton L.
Markowitz, Sanford D.
Desai, Amar B.
15-PGDH regulates hematopoietic and gastrointestinal fitness during aging
title 15-PGDH regulates hematopoietic and gastrointestinal fitness during aging
title_full 15-PGDH regulates hematopoietic and gastrointestinal fitness during aging
title_fullStr 15-PGDH regulates hematopoietic and gastrointestinal fitness during aging
title_full_unstemmed 15-PGDH regulates hematopoietic and gastrointestinal fitness during aging
title_short 15-PGDH regulates hematopoietic and gastrointestinal fitness during aging
title_sort 15-pgdh regulates hematopoietic and gastrointestinal fitness during aging
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119474/
https://www.ncbi.nlm.nih.gov/pubmed/35587945
http://dx.doi.org/10.1371/journal.pone.0268787
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