Comparative tight junction protein expressions in colonic Crohn's disease, ulcerative colitis, and tuberculosis: a new perspective.
We intended to see the pattern of TJ protein expression along with ultrastructural changes in colonic biopsies from patients with Crohn's disease (CD), ulcerative colitis (UC), and tuberculosis (cTB). Colonic biopsies from 11 patients with active CD and ten patients each with active UC and untreated cTB were taken along with biopsies from six patients with irritable bowel syndrome as controls. These were evaluated for expression pattern of key TJ proteins which included claudin-2 as TJ pore-forming protein, claudin-4 as pore-sealing protein, ZO-1 as scaffold protein, and occludin as TJ protein related to cell migration and polarity. Claudin-2 expression was upregulated along the whole length of intercellular junction (ICJ) in biopsies from patients with active CD and UC in comparison to the biopsies from cTB patients and controls, where its expression was limited to the uppermost part of ICJ. There was reduced expression of ZO-1 in UC, CD, and cTB. On transmission electron microscopic examination, the pentalaminar structure of TJs was destroyed in patients with CD and UC but no significant change was seen in those with cTB and in controls. The expression of claudin-2 was distinctly different in active CD and UC in comparison to its expression pattern in patients with cTB and in controls. The redistribution of claudin-2 expression was in accordance with the TJ ultrastructural changes in patients with UC, CD, and cTB. Altered claudin-2 expression, along with destroyed TJs, may result in loss of selective permeability in patients with UC and CD.
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Prasenjit
P
Das
Pooja
P
Goswami
Tapash K
TK
Das
Tapas
T
Nag
Vishnubhatla
V
Sreenivas
Vineet
V
Ahuja
Subrat K
SK
Panda
Siddhartha Datta
SD
Gupta
Govind K
GK
Makharia
D000328:Adult; D062506:Claudin-4; D057167:Claudins / Q000096:biosynthesis; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis; D046529:Microscopy, Electron, Transmission; D062793:Occludin; D010750:Phosphoproteins / Q000096:biosynthesis; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure*; D014385:Tuberculosis, Gastrointestinal / Q000378:metabolism* / Q000473:pathology; D062826:Zonula Occludens-1 Protein
C491875:CLDN2 protein, human; C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein