Publication date: April 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 4
Author(s): Hina Mir, Avtar S. Meena, Kamaljit K. Chaudhry, Pradeep K. Shukla, Ruchika Gangwar, Bhargavi Manda, Mythili K. Padala, Le Shen, Jerrold R. Turner, Paula Dietrich, Ioannis Dragatsis, RadhaKrishna Rao
BackgroundDisruption of epithelial tight junctions (TJ), gut barrier dysfunction and endotoxemia play crucial role in the pathogenesis of alcoholic tissue injury. Occludin, a transmembrane protein of TJ, is depleted in colon by alcohol. However, it is unknown whether occludin depletion influences alcoholic gut and liver injury.MethodsWild type (WT) and occludin deficient (Ocln−/−) mice were fed 1–6% ethanol in Lieber–DeCarli diet. Gut permeability was measured by vascular-to-luminal flux of FITC-inulin. Junctional integrity was analyzed by confocal microscopy. Liver injury was assessed by plasma transaminase, histopathology and triglyceride analyses. The effect of occludin depletion on acetaldehyde-induced TJ disruption was confirmed in Caco-2 cell monolayers.ResultsEthanol feeding significantly reduced body weight gain in Ocln−/− mice. Ethanol increased inulin permeability in colon of both WT and Ocln−/− mice, but the effect was 4-fold higher in Ocln−/− mice. The gross morphology of colonic mucosa was unaltered, but ethanol disrupted the actin cytoskeleton, induced redistribution of occludin, ZO-1, E-cadherin and β-catenin from the junctions and elevated TLR4, which was more severe in Ocln−/− mice. Occludin knockdown significantly enhanced acetaldehyde-induced TJ disruption and barrier dysfunction in Caco-2 cell monolayers. Ethanol significantly increased liver weight and plasma transaminase activity in Ocln−/− mice, but not in WT mice. Histological analysis indicated more severe lesions and fat deposition in the liver of ethanol-fed Ocln−/− mice. Ethanol-induced elevation of liver triglyceride was also higher in Ocln−/− mice.ConclusionThis study indicates that occludin deficiency increases susceptibility to ethanol-induced colonic mucosal barrier dysfunction and liver damage in mice.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nG8AUA
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
-
UM-Chor1: establishment and characterization of the first validated clival chordoma cell line. J Neurosurg. 2017 Apr 21;:1-9 Authors:...
-
Publication date: Available online 10 May 2017 Source: Journal of Dairy Science Author(s): R.E. Vibart, M. Tavendale, D. Otter, B.H. Schw...
-
Competency-based psychiatric education for Indian medical undergraduates Vijayalakshmi Pernenkil Archives of Mental Health 2019 20(1):1-2 Be...
-
Related Articles Developmental control of macrophage function. Curr Opin Immunol. 2017 Dec 13;50:64-74 Authors: Bonnardel J, Guillia...
-
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2tcPIjn via IFTTT
-
Abstract: Epidermolytic ichthyosis (EI) is a rare disorder of cornification caused by mutations in KRT1 and KRT10, encoding two suprabasal e...
-
Bloomberg Celgene Settles Whistle-Blower Fraud Suit for $280 Million Bloomberg Even after the FDA approved Thalomid for multiple myelo...
-
Related Articles Chinese version of the Constant-Murley questionnaire for shoulder pain and disability: a reliability and validation ...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου