| 1. |
- Henriksnäs, Johanna, et al.
(författare)
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Impaired mucus-bicarbonate barrier in Helicobacter pylori-infected mice
- 2006
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 291:3, s. G396-G403
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Tidskriftsartikel (refereegranskat)abstract
- To resist the harsh intrinsic milieu, several lines of defense exist in the stomach. The aim of this study was to investigate the effect of the gastric pathogen Helicobacter pylori on these mechanisms in vivo. We used FVB/N mice expressing human alpha-1,3/4-fucosyl transferase ( producing Lewis b epitopes) and inoculated with H. pylori 1. Mice were anesthetized with isoflurane or Hypnorm-midazolam, the stomach was exteriorized, and the surface of the corpus mucosa was exposed. Mucus thickness was measured with micropipettes, juxtamucosal pH (pH(jm)) was measured with pH-sensitive microelectrodes, blood flow was measured with laser-Doppler flowmetry, and mRNA levels of the bicarbonate transporter SLC26A9 were quantified with real-time PCR. The increase in mucosal blood flow seen in response to luminal acid (pH 1.5) in control animals (140 +/- 9% of control) was abolished in infected mice. The firmly adherent mucus layer was significantly thinner in infected mice (31 +/- 2 mu m) than in control mice (46 +/- 5 mu m), and no mucus accumulation occurred in infected mice. pHjm decreased significantly more on exposure to luminal acid in infected mice ( luminal pH 1.5, pH(jm) 2.4 +/- 0.7) than in control mice (pH(jm) 6.4 +/- 0.5). Despite reduced pHjm, SLC26A9 mRNA expression was significantly, by increased 1.9-fold, in infected mice. The reduction in pH(jm) by infection with H. pylori might be due to a reduced firmly adherent mucus layer, increased mucus permeability to H+, and/or inhibition of bicarbonate transport. The upregulation of SLC26A9 in H. pylori-infected epithelium might be a result of continuous inhibition of the transporter, e. g., by ammonium, a H. pylori product, which has been previously shown to inhibit SLC26A9.
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| 2. |
- Singh, Anurag Kumar, et al.
(författare)
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The switch of intestinal Slc26 exchangers from anion absorptive to HCO3- secretory mode is dependent on CFTR anion channel function
- 2010
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 298:5, s. C1057-C1065
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Tidskriftsartikel (refereegranskat)abstract
- Singh AK, Riederer B, Chen M, Xiao F, Krabbenhoft A, Engelhardt R, Nylander O, Soleimani M, Seidler U. The switch of intestinal Slc26 exchangers from anion absorptive to HCO3- secretory mode is dependent on CFTR anion channel function. Am J Physiol Cell Physiol 298: C1057-C1065, 2010. First published February 17, 2010; doi:10.1152/ajpcell.00454.2009.-CFTR has been recognized to function as both an anion channel and a key regulator of Slc26 anion transporters in heterologous expression systems. Whether this regulatory relationship between CFTR and Slc26 transporters is seen in native intestine, and whether this effect is coupled to CFTR transport function or other features of this protein, has not been studied. The duodena of anesthetized CFTR-, NHE3-, Slc26a6-, and Scl26a3-deficient mice and wild-type (WT) littermates were perfused, and duodenal bicarbonate (HCO3-) secretion (DBS) and fluid absorptive or secretory rates were measured. The selective NHE3 inhibitor S1611 or genetic ablation of NHE3 significantly reduced fluid absorptive rates and increased DBS. Slc26a6 (PAT1) or Slc26a3 (DRA) ablation reduced the S1611-induced DBS increase and reduced fluid absorptive rates, suggesting that the effect of S1611 or NHE3 ablation on HCO3- secretion may be an unmasking of Slc26a6- and Slc26a3-mediated Cl-/HCO3- exchange activity. In the absence of CFTR expression or after application of the CFTR(inh)-172, fluid absorptive rates were similar to those of WT, but S1611 induced virtually no increase in DBS, demonstrating that CFTR transport activity, and not just its presence, is required for Slc26-mediated duodenal HCO3- secretion. A functionally active CFTR is an absolute requirement for Slc26-mediated duodenal HCO3- secretion, but not for Slc26-mediated fluid absorption, in which these transporters operate in conjunction with the Na+/H+ exchanger NHE3. This suggests that Slc26a6 and Slc26a3 need proton recycling via NHE3 to operate in the Cl- absorptive mode and Cl- exit via CFTR to operate in the HCO3- secretory mode.
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| 3. |
- Xiao, Fang, et al.
(författare)
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Slc26a3 deficiency is associated with loss of colonic HCO3 (-) secretion, absence of a firm mucus layer, and barrier impairment in mice.
- 2014
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 211:1, s. 161-175
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Tidskriftsartikel (refereegranskat)abstract
- DRA (downregulated in adenoma, Slc26a3) is a member of the SLC26 family of anion transporters, which is mutated in congenital chloride diarrhoea (CLD). Besides Cl(-) -rich diarrhoea, CLD patients also have a higher than average incidence of intestinal inflammation. In a search for potential explanations for this clinical finding, we investigated colonic electrolyte transport, the mucus layer, and susceptibility against dextran sodium sulphate (DSS)-induced colitis in Slc26a3(-/-) mice.
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