15-PGDH regulates hematopoietic and gastrointestinal fitness during aging

Won Jin Ho; Julianne N.P. Smith; Young Soo Park; Matthew Hadiono; Kelsey Christo; Alvin Jogasuria; Yongyou Zhang; Alyssia V. Broncano; Lakshmi Kasturi; Dawn M. Dawson; Stanton L. Gerson; Sanford D. Markowitz; Amar B. Desai

doi:10.1371/journal.pone.0268787

15-PGDH regulates hematopoietic and gastrointestinal fitness during aging

Won Jin Ho, Julianne N.P. Smith, Young Soo Park, Matthew Hadiono, Kelsey Christo, Alvin Jogasuria, Yongyou Zhang, Alyssia V. Broncano, Lakshmi Kasturi, Dawn M. Dawson, Stanton L. Gerson, Sanford D. Markowitz, Amar B. Desai

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	e0268787
Journal	PloS one
Volume	17
Issue number	5 May
DOIs	https://doi.org/10.1371/journal.pone.0268787
State	Published - May 2022

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title = "15-PGDH regulates hematopoietic and gastrointestinal fitness during aging",

abstract = "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{\textquoteright} 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.",

author = "Ho, {Won Jin} and Smith, {Julianne N.P.} and Park, {Young Soo} and Matthew Hadiono and Kelsey Christo and Alvin Jogasuria and Yongyou Zhang and Broncano, {Alyssia V.} and Lakshmi Kasturi and Dawson, {Dawn M.} and Gerson, {Stanton L.} and Markowitz, {Sanford D.} and Desai, {Amar B.}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2022 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2022",

month = may,

doi = "10.1371/journal.pone.0268787",

language = "English (US)",

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AU - Ho, Won Jin

AU - Smith, Julianne N.P.

AU - Park, Young Soo

AU - Hadiono, Matthew

AU - Christo, Kelsey

AU - Jogasuria, Alvin

AU - Zhang, Yongyou

AU - Broncano, Alyssia V.

AU - Kasturi, Lakshmi

AU - Dawson, Dawn M.

AU - Gerson, Stanton L.

AU - Markowitz, Sanford D.

AU - Desai, Amar B.

N1 - Publisher Copyright: Copyright: © 2022 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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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15-PGDH regulates hematopoietic and gastrointestinal fitness during aging

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