Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: effect of bombesin and neurotensin.
OBJECTIVE
To investigate the influence of experimental obstructive jaundice and exogenous bombesin (BBS) and neurotensin (NT) administration on the expression of the tight junction (TJ)-protein claudin-4 in intestinal epithelium of rats.


METHODS
Forty male Wistar rats were randomly divided into five groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL+BBS (30 microg/kg per d), V = BDL+NT (300 microg/kg per d). At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium.


RESULTS
Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. Claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia.


CONCLUSIONS
Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium, which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.
Assimakopoulos
Stelios F
SF
Department of Internal Medicine, School of Medicine, University of Patras, Greece. sassim@upatras.gr
Vagianos
Constantine E
CE
Charonis
Aristides S
AS
Alexandris
Ilias H
IH
Spiliopoulou
Iris
I
Thomopoulos
Konstantinos C
KC
Nikolopoulou
Vassiliki N
VN
Scopa
Chrisoula D
CD
D000818:Animals; D001663:Bilirubin / Q000097:blood; D001839:Bombesin / Q000494:pharmacology* / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D062506:Claudin-4; D004731:Endotoxins / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000187:drug effects* / Q000473:pathology; D041781:Jaundice, Obstructive / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D009496:Neurotensin / Q000494:pharmacology* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000737:chemistry / Q000502:physiology
D062506:Claudin-4; D004731:Endotoxins; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D009496:Neurotensin; D001839:Bombesin; D001663:Bilirubin