title: Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn's disease?
abstract: Abnormalities of transmembrane and cytoplasmic proteins of tight junctions (TJ) have been implicated in pathogenesis of both celiac (CeD) and Crohn's diseases (CD). Since disease pathogenesis in CeD and CD are different, we planned to study if there is any differential expression pattern of TJ marker proteins and ultrastructural changes, respectively, in duodenal villi vs crypts. Endoscopic duodenal biopsies from treatment naïve patients with CeD (n = 24), active CD (n = 28), and functional dyspepsia (as controls, n = 15), both at baseline and 6 months after treatment, were subjected to light microscopic analysis (modified Marsh grading); immune-histochemical staining and Western blot analysis to see the expression of key TJ proteins [trans-membrane proteins (claudin-2, claudin-3, claudin-4, occludin, and JAM) and cytoplasmic protein (ZO-1)]. Transmission electron microscopy and image analysis of the TJs were also performed. There was significant overexpression of claudin-2 (pore-forming) and occludin (protein maintaining cell polarity) with under-expression of claudin-3 and claudin-4 (pore-sealing proteins) in treatment naïve CeD and active CD with simultaneous alteration in ultrastructure of TJs such as loss of penta-laminar structure and TJ dilatation. Normalization of some of these TJ proteins was noted 6 months after treatment. These changes were not disease specific and were not different in duodenal villi and crypts. Overexpression of pore-forming and under-expression of pore-sealing TJ proteins lead to dilatation of TJ. These changes are neither disease specific nor site specific and the end result of mucosal inflammation.
authors.affiliation: Department of Gastroenterology and Human Nutrition, All India institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Goswami
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Das
authors.forename: Anil K
authors.initials: AK
authors.lastname: Verma
authors.forename: Shyam
authors.initials: S
authors.lastname: Prakash
authors.forename: T K
authors.initials: TK
authors.lastname: Das
authors.forename: T C
authors.initials: TC
authors.lastname: Nag
authors.forename: Vineet
authors.initials: V
authors.lastname: Ahuja
authors.forename: Siddhartha Datta
authors.initials: SD
authors.lastname: Gupta
authors.forename: Govind K
authors.initials: GK
authors.lastname: Makharia
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002446:Celiac Disease / Q000473:pathology* / Q000503:physiopathology; D062446:Claudin-2 / Q000096:biosynthesis; D057167:Claudins / Q000096:biosynthesis; D003424:Crohn Disease / Q000473:pathology* / Q000503:physiopathology; D004386:Duodenum / Q000473:pathology / Q000648:ultrastructure*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D062726:Junctional Adhesion Molecules / Q000096:biosynthesis; D008297:Male; D046529:Microscopy, Electron, Transmission; D062793:Occludin / Q000096:biosynthesis; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure*; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis
chemical_list: D062446:Claudin-2; D057167:Claudins; D062726:Junctional Adhesion Molecules; D062793:Occludin; D062826:Zonula Occludens-1 Protein