Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation

Dublineau, Isabelle; Lebrun, Fabienne; Grison, Stéphane; Griffiths, N. M.

doi:10.1139/y03-129

Cited by 23 publications

(15 citation statements)

References 43 publications

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“…17 This effect is also demonstrated in vivo, in which irradiation causes a drastic loss of ␤-catenin staining in the gastrointestinal epithelium. 41 In contrast to these studies, we found an increase in ␤-catenin protein abundance and transcriptional activity after irradiation in both mouse and human fibroblast cell cultures, as well as during wound healing in vivo. These data suggest a different response to irradiation in mesenchymal cell types than in many epithelial cell types.…”

Section: Discussioncontrasting

confidence: 99%

β-Catenin Is a Mediator of the Response of Fibroblasts to Irradiation

Gurung

Uddin

Hill

et al. 2009

The American Journal of Pathology

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Radiation causes soft tissue complications that include fibrosis and deficient wound healing. ␤-Catenin , a key component in the canonical Wnt-signaling pathway , is activated in fibrotic processes and wound repair and , as such , could play a role in mediating cellular responses to irradiation. ␤-Catenin can form a transcriptionally active complex with members of the Tcf family. A reporter mouse model , in addition to human cell cultures , was used to demonstrate that ionizing radiation activates ␤-catenin-mediated , Tcf-dependent transcription both in vitro and in vivo. Furthermore , radiation activates ␤-catenin via a Wnt-mediated mechanism , as in the presence of dickkopf-1 , an inhibitor of Wnt receptor activation , ␤-catenin levels did not increase after irradiation. Fibroblast cell cultures were derived from mice expressing either null or stabilized ␤-catenin alleles. Cells expressing stabilized ␤-catenin alleles had a higher proliferation rate and formed more colony-forming units than wild-type or null cells after irradiation. Wound healing was studied in these same mice after irradiation. There was a positive correlation between the tensile strength of the wound , the expression levels of type 1 collagen in the skin , and ␤-catenin levels. Mice treated with lithium showed increased ␤-catenin levels and increased wound strength. ␤-Catenin mediates the effects of ionizing radiation in fibroblasts , and its modulation has the potential to decrease the severity of radiation-induced soft tissue complications.

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Section: Discussioncontrasting

confidence: 99%

β-Catenin Is a Mediator of the Response of Fibroblasts to Irradiation

Gurung

Uddin

Hill

et al. 2009

The American Journal of Pathology

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“…Concerning intestinal permeability, results obtained in our laboratory have shown that ileal permeability to mannitol and dextran 4000 was enhanced 3 days after a 8-Gy hemibody exposure (Dublineau et al 2002), and this is consistent with increased TCDC intestinal passive absorption efficiency. Increased permeability to chenodeoxycholate may also partly occur in the colon, as has already been shown (Thomson et al 1984).…”

Section: Discussionsupporting

confidence: 77%

Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

Scanff

Souidi²,

Grison³

et al. 2004

Can. J. Physiol. Pharmacol.

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The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed.

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“…The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions as evidenced by immunohistochemical analyses of junctional proteins (ZO-1 and beta-catenin) observed by confocal microscope. A disorganization of the localization for ZO-1 and beta-catenin was also observed [31].…”

Section: Radiation Injurymentioning

confidence: 91%