Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

BACKGROUND/AIMS: Postoperative ileus (POI) is characterized by impaired propulsive function of the gastrointestinal tract after surgery. Although inflammation is considered to be an important pathogenesis of POI, significant data are lacking. We aim to correlate the recovery time of postoperative dysmotility with that of inflammation and mucosal permeability. METHODS: An experimental POI model of guinea pig was used. Contractile activity of the circular muscle of the stomach, jejunum, ileum, and proximal colon was measured through a tissue bath study. Inflammatory cells were counted, and the expression of calprotectin and tryptase were analyzed. The expression of protease-activated receptor 2 (PAR-2), claudin-1, and claudin-2 were analyzed with immunofluorescence. RESULTS: The small bowel and colon showed decreased contractile amplitude in the POI groups compared to control. In contrast to the colon, the contractile amplitude of the small bowel significantly recovered in the POI group at 6 hours after the operation compared to the control group. Inflammation was highly significant in the POI groups compared to the control and sham groups, especially in the colon. Immunofluorescence showed increased PAR-2 expression in the POI groups compared to sham. The decreased claudin-1 expression and increased claudin-2 expression may suggest increased mucosal permeability of the small bowel and colon in the POI groups. CONCLUSIONS: Increased inflammation and mucosal permeability may play an important role in the differential recovery stages in POI. These data may provide further insights into the pathophysiology and potential new therapeutic prospects of POI.

Role of TGF-β1 in Sertoli cells and tight junction / 中华男科学杂志

Objective@#To explore the role of TGF-β1 in the proliferation and apoptosis of Sertoli cells and its effect on the expressions of tight junction-related proteins and genes in rats.@*METHODS@#Rat Sertoli cells were isolated in vitro, primarily cultured, and divided into groups A (blank control), B (TGF-β1 receptor blocker), C (TGF-β1), and D (TGF-β1 + receptor blocker). The proliferation and apoptosis of the cells were detected by CCK-8 and flow cytometry, respectively. After establishment of the dual-chamber model for the primary culture of Sertoli cells, the trans-epithelia electrical resistance (TER) value was measured and the relative expressions of Occludin, ZO-1 and Claudin Ⅱ determined by RT-PCR and Western blot.@*RESULTS@#The OD value of the proliferation of the Sertoli cells was markedly higher in group C than in groups A and D (0.79 ± 0.04 vs 0.66 ± 0.05 and 0.68 ± 0.02, P0.05). The TER value was dramatically decreased in group C as compared with groups A and D (［176.37 ± 16.61］ vs ［281.42 ± 9.83］ and ［254.37 ± 13.55］ /cm2, P0.05) or their protein expressions (F = 0.28 and 1.31, P>0.05). Both the mRNA and protein expressions of Occludin were markedly lower in group C than in A and D (P<0.01 and P<0.05), with statistically significant differences among the four groups (F = 6.86 and 6.87, P<0.01).@*CONCLUSIONS@#TGF-β1 can promote the proliferation of Sertoli cells in rats and act on the tight junction of the cells by regulating the expression of Occludin.

Claudin-1, -2, -4, and -5: comparison of expression levels and distribution in equine tissues

Claudins, which are known as transmembrane proteins play an essential role in tight junctions (TJs) to form physical barriers and regulate paracellular transportation. To understand equine diseases, it is helpful to measure the tissue-specific expression of TJs in horses. Major equine diseases such as colic and West Nile cause damage to TJs. In this study, the expression level and distribution of claudin-1, -2, -4, and -5 in eight tissues were assessed by Western blotting and immunohistochemistry methods. Claudin-1 was primarily identified in the lung, duodenum, and uterus, claudin-2 was evenly observed in equine tissues, claudin-4 was abundantly detected in the liver, kidney and uterus, and claudin-5 was strongly expressed in the lung, duodenum, ovary, and uterus, as determined by Western blotting method. The localization of equine claudins was observed by immunohistochemistry methods. These findings provide knowledge regarding the expression patterns and localization of equine claudins, as well as valuable information to understand tight junction-related diseases according to tissue specificity and function of claudins in horses.

Expression of tight junction protein claudin-2 in renal tissues and its significance in children with acute kidney injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To examine changes in expression of tight junction protein claudin-2 in the renal tissues of children with acute kidney injury (AKI), and to investigate the relationship of claudin-2 expression with renal pathological lesion and renal functional lesion.</p><p><b>METHODS</b>Twenty-four children who were diagnosed with AKI and had renal biopsies between December 2009 and December 2011 were included in the study. These patients were divided into mild AKI (n=7) and severe AKI groups (n=17). Children with isolated hematuria whose renal biopsy showed minor glomerular lesion were selected as the control group. Serum creatinine levels were measured by automatic biochemical analyzer. Tubulointerstitial damage was evaluated by renal pathological scores and expression of claudin-2 was examined by immunohistochemistry. The correlations of claudin-2 expression with renal pathological score and serum creatinine level were assessed by Pearson correlation analysis.</p><p><b>RESULTS</b>The mild and severe AKI groups had significantly higher serum creatinine levels than the control group (190 ± 68 μmol/L and 477 ± 128 μmol/L vs 29 ± 7 μmol/L, P<0.01), and the severe AKI group had a significantly higher serum creatinine level than the mild AKI group (P<0.01). The tubulointerstitial damage score was significantly lower in the mild AKI group than in the severe AKI group (10.4 ± 1.7 vs 14.0 ± 1.5; P<0.05). The mild and severe AKI groups had significantly smaller areas of claudin-2 expression than the control group (5.0 ± 0.5% and 3.7 ± 0.7% vs 8.0 ± 0.7%; P<0.01), and the severe AKI group had a significantly smaller area of claudin-2 expression than the mild AKI group (P<0.01). The area of claudin-2 expression was negatively correlated with serum creatinine level and tubulointerstitial damage score (r=-0.809 and -0.903; P<0.01).</p><p><b>CONCLUSIONS</b>There are changes in the distribution and expression of claudin-2 in proximal tubular epithelial cells among children with AKI, and claudin-2 expression is closely related to renal pathological lesion and renal functional lesion.</p>

Relevance of Ultrastructural Alterations of Intercellular Junction Morphology in Inflamed Human Esophagus

BACKGROUND/AIMS: Detailed characterization of the ultrastructural morphology of intercellular space in gastroesophageal reflux disease has not been fully studied. We aimed to investigate whether subtle alteration in intercellular space structure and tight junction proteins might differ among patients with gastroesophageal reflux disease. METHODS: Esophageal biopsies at 5 cm above the gastroesophageal junction were obtained from 6 asymptomatic controls, 10 patients with reflux symptoms but without erosions, and 18 patients with erosions. The biopsies were morphologically evaluated by transmission electron microscopy, and by using immunohistochemistry for tight junction proteins (claudin-1 and claudin-2 proteins). RESULTS: The expressions of tight junction proteins did not differ between asymptomatic controls and gastroesophageal reflux disease patients. In patients with gastroesophageal reflux disease, altered desmosomal junction morphology was only found in upper stratified squamous epithelium. Dilated intercellular space occurred only in upper stratified squamous epithelium and in patients with erosive esophagitis. CONCLUSIONS: This study suggests that dilated intercellular space may not be uniformly present inside the esophageal mucosa and predominantly it is located in upper squamous epithelium. Presence of desmosomal junction alterations is associated with increased severity of gastroesophageal reflux disease. Besides dilated intercellular space, subtle changes in ultrastructural morphology of intercellular space allow better identification of inflamed esophageal mucosa relevant to acid reflux.