Solute transporters and aquaporins are impaired in celiac disease

Abstract

Background information. Celiac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible subjects by gluten ingestion. Diarrhoea, weight loss and malabsorption represent the major clinical presentation of the disease. Here we examined the possible alteration in the expression and localization of water channels [AQPs (aquaporins)] and some solute transporters in duodenal mucosa of celiac disease patients. Duodenal biopsies from untreated celiacs, treated celiacs, healthy controls and disease controls were considered in the present study. The expressions of some AQPs and transporter mRNAs in human duodenal biopsies were determined by semi‐quantitative RT—PCR (reverse transcription PCR) and real‐time RT—PCR. The localization of AQPs 3, 7 and 10 and of SGLT1 (Na+/glucose co‐transporter 1), PEPT1 (H+/oligopeptide transporter 1) and NHE3 (Na+/H+ exchanger 3) was evaluated by immunohistochemistry. Results. AQPs 3, 7, 10 and 11, SGLT, PEPT and NHE, CFTR (cystic fibrosis transmembrane conductance regulator) and NKCC (Na‐K‐2Cl co‐transporter) mRNAs were expressed in duodenal biopsies of healthy controls, treated celiac patients and disease controls. The expression of transcripts was virtually absent in duodenal biopsies of untreated celiac disease patients except for CFTR and NKCC. In healthy controls, immunohistochemistry revealed a labelling in the apical membrane of surface epithelial cells of the duodenum. The immunolabelling was heavily reduced or absent in untreated celiac patients, while it was normal in patients consuming a gluten‐free diet for at least 12 months. Conclusions. Our results indicate that the main routes for water and solute absorption are deficient in celiac disease and may play a role in the onset of malabsorption symptoms.

Human Intestinal PEPT1 Transporter Expression and Localization in Preterm and Term Infants

“…The gene expression of PEPT1 in neonatal intestine samples was confirmed by immunohistochemical staining showing protein PEPT1 expression in the brush border of the enterocyte. Localization of PEPT1 in the apical part along the brush border of villus epithelial cells was comparable with staining in human adolescents (this study) and adults, rat, and mice (Groneberg et al, 2001;Hussain et al, 2002;Ziegler et al, 2002;Laforenza et al, 2010).…”

Aquaporins in Health and Disease: An Overview Focusing on the Gut of Different Species

“…A role for AQPs was also investigated in celiac disease, another intestinal inflammatory disorder induced in genetically susceptible subjects by gluten ingestion [31]. Studies in this regard have demonstrated a dramatic reduction in both AQP mRNA and protein expression combined with a reduced activity of principal solute transporters in the villus (i.e., SGLT1, PEPT1, and NHE3).…”

Aquaporin expression in the Japanese medaka (Oryzias latipes, Temminck & Schlegel) in FW and SW: challenging the paradigm for intestinal water transport?

“…Its subcellular localization is controversial (Hatakeyama et al, 2001;Ishibashi et al, 2002;Li et al, 2005;Laforenza et al, 2010), and surprisingly, it is a pseudogene in mouse (Morinaga et al, 2002). The AQP10 protein was reported in the brush-border membrane of absorptive enterocytes of the upper villus Laforenza et al, 2010), whereas other authors have demonstrated the presence of two AQP10 isoforms, one located in gastroentero-pancreatic endocrine cells and another truncated form (named AQP10v), in capillary endothelial cells of villi (Li et al, 2005). In humans, zebrafish and eel the ortholog is permeable to water, glycerol and urea (Ishibashi et al, 2002;MacIver et al, 2009;Tingaud-Sequeira et al, 2010).…”