@article{nighot_nighot_ma_malinowska_shull_cuppoletti_blikslager_2015, title={Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion}, volume={10}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0138174}, DOI={10.1371/journal.pone.0138174}, abstractNote={The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84–95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.}, number={9}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Nighot, Meghali P. and Nighot, Prashant K. and Ma, Thomas Y. and Malinowska, Danuta H. and Shull, Gary E. and Cuppoletti, John and Blikslager, Anthony T.}, editor={Guerrero-Hernandez, AgustínEditor}, year={2015}, month={Sep}, pages={e0138174} }
 @article{nighot_young_nighot_rawat_sung_maharshak_plevy_ma_blikslager_2013, title={Chloride Channel ClC-2 is a Key Factor in the Development of DSS-induced Murine Colitis}, volume={19}, ISSN={1078-0998}, url={http://dx.doi.org/10.1097/MIB.0b013e3182a82ae9}, DOI={10.1097/mib.0b013e3182a82ae9}, abstractNote={Background:Previously, it was shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury. Methods:The role of ClC-2 was investigated in TJ barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2 knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was measured electrophysiologically and by transepithelial mannitol fluxes. Selected TJ and associated proteins were Western blotted, cytokines were measured using quantitative PCR, and human colonic biopsies were examined with immunohistochemistry. Results:ClC-2−/− mice had a higher disease activity index, higher histological scores, and increased paracellular permeability compared with wild-type mice when treated with DSS. DSS-treated ClC-2−/− mice had increased claudin-2 expression, greater loss of occludin in the membrane, increased association of occludin with caveolin-1, and significantly increased tumor necrosis factor-&agr; and interleukin-1&bgr; messenger RNA. ClC-2 knockdown in human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance in the event of epithelial injury. The restoration of colonic barrier function after DSS colitis was delayed in ClC-2−/− mice. In human colonic biopsies, the protein and messenger RNA expression of ClC-2 was found to be reduced in patients with ulcerative colitis. Conclusions:ClC-2 plays a critical role in experimental colitis in that its absence increases disease activity, reduces barrier function and recovery, and perturbs TJs. Furthermore, ClC-2 expression is markedly reduced in the colon of human patients with ulcerative colitis.}, number={13}, journal={Inflammatory Bowel Diseases}, publisher={Oxford University Press (OUP)}, author={Nighot, Prashant and Young, Karen and Nighot, Meghali and Rawat, Manmeet and Sung, Eui J. and Maharshak, Nitsan and Plevy, Scott E. and Ma, Thomas and Blikslager, Anthony}, year={2013}, month={Dec}, pages={2867–2877} }
 @article{nighot_moeser_ueno_blikslager, title={Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa}, volume={18}, number={34}, journal={World Journal of Gastroenterology}, author={Nighot, M. and Moeser, A. and Ueno, R. and Blikslager, A.}, pages={4684–4692} }