Intestinal epithelial barrier disfunction in patients with chronic intestinal pseudo-obstruction

Background: Chronic intestinal pseudo-obstruction (CIPO) is a rare condition characterized by gastrointestinal (GI) impairment that is so severe to cause a clinical picture suggestive of a mechanical obstruction in the absence of any occlusion. Although degenerative or inflammatory neuro-interstitial cells of Cajal (ICC)-muscular abnormalities are the main pathogenetic mechanisms underlying gut dysfunction, other factors, i.e. intestinal epithelial barrier (IEB) abnormalities, may represent the initial insult contributing to symptoms and clinical manifestations. Aim: To assess the expression of occludin and zonula occludens-1 (ZO-1), two major components of tight junctions (TJs), as markers of IEB integrity in patients with CIPO. Methods: A number of n=26 clinically and histopathologically well characterized CIPO pts (15 F; age range: 16 - 75 yrs) were studied. CIPO cases were subdivided according to the histopathological analysis (IHC) in 3 groups: A) apparently normal n=7; B) inflamed n=8; C) degenerative n=10. Patients (n=8; 3 F, age range: 48 - 73 yrs) undergoing elective surgery for uncomplicated neoplastic diseases served as controls. CIPO and control jejunal full thickness biopsies were processed to assess occludin and ZO-1 mRNA and protein expression using q-PCR and WB. Results: Compared to controls, total occludin protein showed a marked decrease in CIPO pts (P