Prosurvival and antiapoptotic effects of PGE2in radiation injury are mediated by EP2 receptor in intestine

2003 ◽  
Vol 284 (3) ◽  
pp. G490-G498 ◽  
Author(s):  
Courtney W. Houchen ◽  
Mark A. Sturmoski ◽  
Shrikant Anant ◽  
Richard M. Breyer ◽  
William F. Stenson
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Cross Section ◽  
Radiation Injury ◽  
Biological Activities ◽  
Receptor Expression ◽  
Apoptotic Cells ◽  
Wild Type ◽  
Γ Irradiation ◽  
Stem Cell Survival

The biological activities of PGE2 are mediated through EP receptors (EP1–EP4), plasma membrane G protein-coupled receptors that differ in ligand binding and signal-transduction pathways. We investigated gastrointestinal EP2 receptor expression in adult mice before and after radiation injury and evaluated intestinal stem cell survival and crypt epithelial apoptosis after radiation injury in EP2 null mice. EP2 was expressed throughout the gut. Intestinal EP2 mRNA increased fivefold after γ-irradiation. Crypt survival was diminished in EP2 −/− mice (4.06 crypts/cross section) compared with wild-type littermates (8.15 crypts/cross section). Radiation-induced apoptosis was significantly increased in EP2 −/− mice compared with wild-type littermates. Apoptosis was 1.6-fold higher in EP2 −/− mice (5.9 apoptotic cells/crypt) than in wild-type mice (3.5 apoptotic cells/crypt). The EP2receptor is expressed in mouse gastrointestinal epithelial cells and is upregulated following radiation injury. The effects of PGE2on both crypt epithelial apoptosis and intestinal crypt stem cell survival are mediated through the EP2 receptor.

Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury

2000 ◽  
Vol 279 (5) ◽  
pp. G858-G865 ◽  
Author(s):  
Courtney W. Houchen ◽  
William F. Stenson ◽  
Steven M. Cohn
Keyword(s):  
Stem Cell ◽  
Epithelial Cell ◽  
Cell Survival ◽  
Cell Fate ◽  
Radiation Injury ◽  
Wild Type ◽  
Stem Cell Survival ◽  
Normal Intestine ◽  
Cox 2 ◽  
Cox 1

Prostaglandins may play an important role in regulating normal renewal of gastrointestinal epithelium, epithelial injury repair, and initiation or progression of intestinal neoplasia. Synthesis of prostaglandins is catalyzed by either of two cyclooxygenase isoforms, Cox-1 and Cox-2. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, Cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation and in adenomas and carcinomas. To determine directly whether prostaglandins synthesized by Cox-1 or Cox-2 regulate crypt epithelial cell fate after genotoxic or cytotoxic injury, we examined apoptosis, prostaglandin synthesis, and crypt stem cell survival after γ-irradiation in Cox-1−/− and Cox-2−/− mice. Cox-1−/− mice had increased crypt epithelial cell apoptosis and decreased clonogenic stem cell survival compared with wild-type littermates. PGE2synthesis was also diminished in Cox-1−/− mice compared with wild-type controls in unstressed intestine and after radiation injury. In contrast, apoptosis, stem cell survival, and intestinal PGE2 synthesis in Cox-2−/− mice after irradiation were the same as in wild-type littermates. Crypt stem cell survival after irradiation was inhibited by a highly specific neutralizing antibody to PGE2, suggesting that this prostaglandin mediates stem cell fate in vivo. These data suggest that prostaglandins synthesized by Cox-1 regulate multiple steps that determine the fate of crypt epithelial cell after genotoxic or cytotoxic injury.

FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury

1999 ◽  
Vol 276 (1) ◽  
pp. G249-G258 ◽  
Author(s):  
Courtney W. Houchen ◽  
Robert J. George ◽  
Mark A. Sturmoski ◽  
Steven M. Cohn
Keyword(s):  
Small Intestine ◽  
Stem Cell ◽  
Cell Survival ◽  
Wound Repair ◽  
Radiation Injury ◽  
Immunohistochemical Analysis ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Γ Irradiation ◽  
Stem Cell Survival

Fibroblast growth factors (FGFs) have mitogenic activity toward a wide variety of cells of mesenchymal, neuronal, and epithelial origin and regulate events in normal embryonic development, angiogenesis, wound repair, and neoplasia. FGF-2 is expressed in many normal adult tissues and can regulate migration and replication of intestinal epithelial cells in culture. However, little is known about the effects of FGF-2 on intestinal epithelial stem cells during either normal epithelial renewal or regeneration of a functional epithelium after injury. In this study, we investigated the expression of FGF-2 in the mouse small intestine after irradiation and determined the effect of exogenous FGF-2 on crypt stem cell survival after radiation injury. Expression of FGF-2 mRNA and protein began to increase at 12 h after γ-irradiation, and peak levels were observed from 48 to 120 h after irradiation. At all times after irradiation, the higher molecular mass isoform (∼24 kDa) of FGF-2 was the predominant form expressed in the small intestine. Immunohistochemical analysis of FGF-2 expression after radiation injury demonstrated that FGF-2 was predominantly found in the mesenchyme surrounding regenerating crypts. Exogenous recombinant human FGF-2 (rhFGF-2) markedly enhanced crypt stem cell survival when given before irradiation. We conclude that expression of FGF-2 is induced by radiation injury and that rhFGF-2 can enhance crypt stem cell survival after subsequent injury.

scholarly journals Prostaglandin E2 Increases Hematopoietic Stem Cell Survival and Accelerates Hematopoietic Recovery After Radiation Injury

Stem Cells ◽  
2013 ◽  
Vol 31 (2) ◽  
pp. 372-383 ◽  
Author(s):  
Rebecca L. Porter ◽  
Mary A. Georger ◽  
Olga Bromberg ◽  
Kathleen E. McGrath ◽  
Benjamin J. Frisch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prostaglandin E2 ◽  
Cell Survival ◽  
Hematopoietic Stem Cell ◽  
Radiation Injury ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Stem Cell Survival

scholarly journals 12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury

Oncotarget ◽  
2017 ◽  
Vol 8 (28) ◽  
pp. 45566-45576 ◽  
Author(s):  
Yaojie Liang ◽  
Hongwei Zhou ◽  
Yibing Yao ◽  
Ailing Deng ◽  
Zhihong Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Radiation Injury ◽  
Intestinal Crypt ◽  
Stem Cell Survival

scholarly journals Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135561 ◽  
Author(s):  
Sripathi M. Sureban ◽  
Randal May ◽  
Dongfeng Qu ◽  
Parthasarathy Chandrakesan ◽  
Nathaniel Weygant ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Radiation Injury ◽  
Intestinal Crypt ◽  
Stem Cell Survival

Mo1304 Dietary Omega-3 Polyunsaturated Fatty Acids Increase Intestinal Crypt Stem Cell Survival Following Radiation Injury

2016 ◽  
Vol 150 (4) ◽  
pp. S692
Author(s):  
Sripathi M. Sureban ◽  
Altaf Mohammed ◽  
Randal May ◽  
Dongfeng Qu ◽  
Parthasarathy Chandrakesan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Stem Cell ◽  
Polyunsaturated Fatty Acids ◽  
Cell Survival ◽  
Radiation Injury ◽  
Omega 3 ◽  
Intestinal Crypt ◽  
Stem Cell Survival

Sa1824 Dietary Pectin Increases Intestinal Crypt Stem Cell Survival Following Radiation Injury

2012 ◽  
Vol 142 (5) ◽  
pp. S-334
Author(s):  
Sripathi M. Sureban ◽  
Randal May ◽  
Dongfeng Qu ◽  
Nathaniel Weygant ◽  
Parthasarathy Chandrakesan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Radiation Injury ◽  
Intestinal Crypt ◽  
Stem Cell Survival

S1685 Inhibition of Notch Signaling Decreases Intestinal Stem Cell Survival Following Radiation Injury

2010 ◽  
Vol 138 (5) ◽  
pp. S-253
Author(s):  
Randal May ◽  
Sripathi M. Sureban ◽  
Stan A. Lightfoot ◽  
James H. Wyche ◽  
Shrikant Anant ◽  
...  
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Cell Survival ◽  
Radiation Injury ◽  
Intestinal Stem Cell ◽  
Stem Cell Survival

The Response of Testes Cells to Low Level, Single dose Helium Particle Irradiation

1982 ◽  
Vol 40 ◽  
pp. 252-253
Author(s):  
D.E. Philpott ◽  
W. Sapp ◽  
C. Williams ◽  
J. Stevenson ◽  
S. Black ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Dose ◽  
B Cell ◽  
Cell Survival ◽  
Spermatogonial Stem Cell ◽  
Low Doses ◽  
Particle Irradiation ◽  
Stem Cell Survival ◽  
Irradiation Injury ◽  
Radio Sensitivity

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.

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