title: Segmental Differences in Radiation-Induced Alterations of Tight Junction-Related Proteins in Non-Human Primate Jejunum, Ileum and Colon.
abstract: Dysfunction of the intestinal epithelial barrier and leakage of luminal antigens and bacteria across the barrier have been linked to various human diseases. Intestinal permeability is regulated by intercellular structures, termed "tight junction" (Tj), which are disrupted after total-body irradiation (TBI). In this study, we investigated radiation-induced alterations in Tj-related proteins in the jejunum, ileum and colon of a non-human primate (NHP) model. NHPs were total-body irradiated with 6.7 and 7.4 Gy and intestines were procured at day 4, 7 and 12. Radiation exposure was found to induce significant increases in claudin-10 mRNA early (day 4) in all three gut segments and claudin-4 mRNA levels were repressed through day 12. TNF-alpha was highly induced in the jejunum and colon at early time points, but little induction was found in the ileum. Claudin-1 was induced only in the colon on day 4 postirradiation. Unlike the colon and jejunum, the ileum levels of claudin-7 were significantly downregulated through day 12 postirradiation. Western blot analysis revealed increased levels of claudin-2 on day 4 and of JAM-1 on day 7 postirradiation in all three gut segments. E-cadherin was downregulated on day 4 postirradiation in all segments, but remained reduced in the jejunum only until day 12. Taken together, these data suggest that exposure to radiation causes segment-specific alterations in the expression of Tj-related proteins. Interruption of Tjs may be a key factor contributing to injury to the intestinal mucosal barrier and increased intestinal permeability.
authors.affiliation: a  Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors.forename: Sarita
authors.initials: S
authors.lastname: Garg
authors.affiliation: a  Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors.forename: Junying
authors.initials: J
authors.lastname: Zheng
authors.affiliation: a  Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors.forename: Junru
authors.initials: J
authors.lastname: Wang
authors.affiliation: b  CIToxLAB, Laval, Quebec, Canada; and.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.affiliation: b  CIToxLAB, Laval, Quebec, Canada; and.
authors.forename: Mylene
authors.initials: M
authors.lastname: Pouliot
authors.affiliation: a  Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas;|c  Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000528:radiation effects; D007408:Intestinal Absorption / Q000502:physiology* / Q000528:radiation effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000528:radiation effects*; D007583:Jejunum / Q000378:metabolism / Q000528:radiation effects; D008253:Macaca mulatta; D008297:Male; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D011829:Radiation Dosage; D062725:Tight Junction Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D062725:Tight Junction Proteins