Mechanisms Underlying Dysregulation of Electrolyte Absorption in Inflammatory Bowel Disease-Associated Diarrhea

Inflammatory Bowel Diseases

Volumn 21, Issue 12, 2015, Pages 2926-2935

  Priyamvada, Shubha ^a   Gomes, Rochelle ^a   Gill, Ravinder K ^a   Saksena, Seema ^a   Alrefai, Waddah A ^a   Dudeja, Pradeep K ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

DRA; intestinal inflammation; NaCl absorption; NHE3

Indexed keywords

ANION; CARRIER PROTEINS AND BINDING PROTEINS; PROTEIN SLC26A3; SODIUM CHLORIDE; SODIUM PROTON EXCHANGE PROTEIN 3; UNCLASSIFIED DRUG; BICARBONATE CHLORIDE ANTIPORTER; ELECTROLYTE; SLC26A3 PROTEIN, HUMAN; SODIUM PROTON EXCHANGE PROTEIN; SODIUM-HYDROGEN EXCHANGER 3;

ABSORPTION; CHLORIDE ABSORPTION; CHLORIDE TRANSPORT; DIARRHEA; DISEASE ASSOCIATION; ELECTROLYTE TRANSPORT; HOMEOSTASIS; HUMAN; INFLAMMATORY BOWEL DISEASE; INTESTINE; ION TRANSPORT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW; SODIUM ABSORPTION; ULCERATIVE COLITIS; COMPLICATION; INTESTINE ABSORPTION; METABOLISM; PATHOPHYSIOLOGY;

CHLORIDE-BICARBONATE ANTIPORTERS; DIARRHEA; ELECTROLYTES; HUMANS; INFLAMMATORY BOWEL DISEASES; INTESTINAL ABSORPTION; INTESTINES; SODIUM CHLORIDE; SODIUM-HYDROGEN ANTIPORTER;

EID: 84948184410     PISSN: 10780998     EISSN: 15364844     Source Type: Journal    
DOI: 10.1097/MIB.0000000000000504     Document Type: Review

References (75)

1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142:46-54.e42; quiz e30.
2. Ellinghaus D, Bethune J, Petersen BS, et al. The genetics of Crohn's disease and ulcerative colitis-status quo and beyond. Scand J Gastroenterol. 2015;50:13-23.
3. Engelhardt KR, Grimbacher B. IL-10 in humans: lessons from the gut, IL-10/IL-10 receptor deficiencies, and IL-10 polymorphisms. Curr Top Microbiol Immunol. 2014;380:1-18.
4. O'Toole A, Korzenik J. Environmental triggers for IBD. Curr Gastroenterol Rep. 2014;16:396.
5. Wenzl HH. Diarrhea in chronic inflammatory bowel diseases. Gastroenterol Clin North Am. 2012;41:651-675.
6. Binder HJ. Mechanisms of diarrhea in inflammatory bowel diseases. Ann N Y Acad Sci. 2009;1165:285-293.
7. Ghishan FK, Kiela PR. Epithelial transport in inflammatory bowel diseases. Inflamm Bowel Dis. 2014;20:1099-1109.
8. Seidler U, Lenzen H, Cinar A, et al. Molecular mechanisms of disturbed electrolyte transport in intestinal inflammation. Ann N Y Acad Sci. 2006; 1072:262-275.
9. Tang Y, Forsyth CB, Keshavarzian A. New molecular insights into inflammatory bowel disease-induced diarrhea. Expert Rev Gastroenterol Hepatol. 2011;5:615-625.
10. Urayama S, Chang EB. Mechanisms and treatment of diarrhea in inflammatory bowel diseases. Inflamm Bowel Dis. 1997;3:114-131.
11. Barkas F, Liberopoulos E, Kei A, et al. Electrolyte and acid-base disorders in inflammatory bowel disease. Ann Gastroenterol. 2013; 26:23-28.
12. Sandle GI. Pathogenesis of diarrhea in ulcerative colitis: new views on an old problem. J Clin Gastroenterol. 2005;39:S49-S52.
13. Gill RK, Dudeja PK. Mechanisms and regulation of NaCl absorption in the human intestine. Recent Research Developments Physiology Trivandrum (India) Res Signpost. 2003:643-677.
14. Field M. Intestinal ion transport and the pathophysiology of diarrhea. J Clin Invest. 2003;111:931-943.
15. Ghishan FK, Kiela PR. Small intestinal ion transport. Curr Opin Gastroenterol. 2012;28:130-134.
16. Martinez-Augustin O, Romero-Calvo I, Suarez MD, et al. Molecular bases of impaired water and ion movements in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15:114-127.
17. Farkas K, Yeruva S, Rakonczay Z Jr, et al. New therapeutic targets in ulcerative colitis: the importance of ion transporters in the human colon. Inflamm Bowel Dis. 2011;17:884-898.
18. Kiela PR, Xu H, Ghishan FK. Apical NA+/H+ exchangers in the mammalian gastrointestinal tract. J Physiol Pharmacol. 2006;57(suppl 7): 51-79.
19. Donowitz M, Ming Tse C, Fuster D. SLC9/NHE gene family, a plasma membrane and organellar family of Na(+)/H(+) exchangers. Mol Aspects Med. 2013;34:236-251.
20. Xu H, Zhang B, Li J, et al. Impaired mucin synthesis and bicarbonate secretion in the colon of NHE8 knockout mice. Am J Physiol Gastrointest Liver Physiol. 2012;303:G335-G343.
21. Schultheis PJ, Clarke LL, Meneton P, et al. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nat Genet. 1998; 19:282-285.
22. Gawenis LR, Stien X, Shull GE, et al. Intestinal NaCl transport in NHE2 and NHE3 knockout mice. Am J Physiol Gastrointest Liver Physiol. 2002; 282:G776-G784.
23. Ledoussal C, Woo AL, Miller ML, et al. Loss of the NHE2 Na(+)/H(+) exchanger has no apparent effect on diarrheal state of NHE3-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1385-G1396.
24. Kato A, Romero MF. Regulation of electroneutral NaCl absorption by the small intestine. Annu Rev Physiol. 2011;73:261-281.
25. Mount DB, Romero MF. The SLC26 gene family of multifunctional anion exchangers. Pflugers Arch. 2004;447:710-721.
26. Alper SL, Sharma AK. The SLC26 gene family of anion transporters and channels. Mol Aspects Med. 2013;34:494-515.
27. Makela S, Kere J, Holmberg C, et al. SLC26A3 mutations in congenital chloride diarrhea. Hum Mutat. 2002;20:425-438.
28. Wedenoja S, Pekansaari E, Hoglund P, et al. Update on SLC26A3 mutations in congenital chloride diarrhea. Hum Mutat. 2011;32: 715-722.
29. Schweinfest CW, Spyropoulos DD, Henderson KW, et al. slc26a3 (dra)-deficient mice display chloride-losing diarrhea, enhanced colonic proliferation, and distinct up-regulation of ion transporters in the colon. J Biol Chem. 2006;281:37962-37971.
30. D'Angelo A, Bluteau O, Garcia-Gonzalez MA, et al. Hepatocyte nuclear factor 1alpha and beta control terminal differentiation and cell fate commitment in the gut epithelium. Development. 2010; 137:1573-1582.
31. Borenshtein D, Schlieper KA, Rickman BH, et al. Decreased expression of colonic Slc26a3 and carbonic anhydrase iv as a cause of fatal infectious diarrhea in mice. Infect Immun. 2009;77:3639-3650.
32. Siddique I, Hasan F, Khan I. Suppression of Na+/H+ exchanger isoform-3 in human inflammatory bowel disease: lack of reversal by 5'-aminosali-cylate treatment. Scand J Gastroenterol. 2009;44:56-64.
33. Sullivan S, Alex P, Dassopoulos T, et al. Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: potential contributors to IBD-associated diarrhea. Inflamm Bowel Dis. 2009;15:261-274.
34. Yeruva S, Farkas K, Hubricht J, et al. Preserved Na(+)/H(+) exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis. Inflamm Bowel Dis. 2010;16:1149-1161.
35. Lohi H, Makela S, Pulkkinen K, et al. Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis. Am J Physiol Gastro-intest Liver Physiol. 2002;283:G567-G575.
36. Yeruva S, Chodisetti G, Luo M, et al. Evidence for a causal link between adaptor protein PDZK1 downregulation and Na/H exchanger NHE3 dysfunction in human and murine colitis. Pflugers Arch. 2015;467: 1795-1807.
37. Rocha F, Musch MW, Lishanskiy L, et al. IFN-gamma downregulates expression of Na(+)/H(+) exchangers NHE2 and NHE3 in rat intestine and human Caco-2/bbe cells. Am J Physiol Cell Physiol. 2001;280: C1224-C1232.
38. Barmeyer C, Harren M, Schmitz H, et al. Mechanisms of diarrhea in the interleukin-2-deficient mouse model of colonic inflammation. Am J Phys-iol Gastrointest Liver Physiol. 2004;286:G244-G252.
39. Amin MR, Malakooti J, Sandoval R, et al. IFN-gamma and TNF-alpha regulate human NHE3 gene expression by modulating the Sp family transcription factors in human intestinal epithelial cell line C2BBe1. Am J Physiol Cell Physiol. 2006;291:C887-C896.
40. Gill RK, Saksena S, Syed IA, et al. Regulation of NHE3 by nitric oxide in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol. 2002;283: G747-G756.
41. Laubitz D, Larmonier CB, Bai A, et al. Colonic gene expression profile in NHE3-deficient mice: evidence for spontaneous distal colitis. Am J Phys-iol Gastrointest Liver Physiol. 2008;295:G63-G77.
42. Kiela PR, Laubitz D, Larmonier CB, et al. Changes in mucosal homeo-stasis predispose NHE3 knockout mice to increased susceptibility to DSS-induced epithelial injury. Gastroenterology. 2009;137:965-975; 975.e1-e10.
43. Larmonier CB, Laubitz D, Hill FM, et al. Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2013;305:G667-G677.
44. Larmonier CB, Laubitz D, Thurston RD, et al. NHE3 modulates the severity of colitis in IL-10-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2011;300:G998-G1009.
45. Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011;140: 1756-1767.
46. Sasaki T, Hiwatashi N, Yamazaki H, et al. The role of interferon-gamma in the pathogenesis of Crohn's disease. Gastroenterol Jpn. 1992;27:29-36.
47. Colgan SP, Parkos CA, Matthews JB, et al. Interferon-gamma induces a cell surface phenotype switch on T84 intestinal epithelial cells. Am J Physiol. 1994;267:C402-C410.
48. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14:329-342.
49. Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. In-flamm Bowel Dis. 2003;9:179-189.
50. Donowitz M, Cha B, Zachos NC, et al. NHERF family and NHE3 regulation. J Physiol. 2005;567:3-11.
51. Lenzen H, Lunnemann M, Bleich A, et al. Downregulation of the NHE3-binding PDZ-adaptor protein PDZK1 expression during cytokine-induced inflammation in interleukin-10-deficient mice. PLoS One. 2012;7:e40657.
52. Bachmann O, Seidler U. News from the end of the gut-how the highly segmental pattern of colonic HCO(3)(-) transport relates to absorptive function and mucosal integrity. Biol Pharm Bull. 2011;34:794-802.
53. Greig E, Sandle GI. Diarrhea in ulcerative colitis. The role of altered colonic sodium transport. Ann N YAcad Sci. 2000;915:327-332.
54. Hawker PC, McKay JS, Turnberg LA. Electrolyte transport across colonic mucosa from patients with inflammatory bowel disease. Gastroenterology. 1980;79:508-511.
55. Sandle GI, Hayslett JP, Binder HJ. Effect of glucocorticoids on rectal transport in normal subjects and patients with ulcerative colitis. Gut. 1986;27:309-316.
56. Edmonds CJ, Pilcher D. Electrical potential difference and sodium and potassium fluxes across rectal mucosa in ulcerative colitis. Gut. 1973;14: 784-789.
57. Sandle GI, Higgs N, Crowe P, et al. Cellular basis for defective electrolyte transport in inflamed human colon. Gastroenterology. 1990;99:97-105.
58. Roediger WE, Lawson MJ, Kwok V, et al. Colonic bicarbonate output as a test of disease activity in ulcerative colitis. J Clin Pathol. 1984;37:704-707.
59. Caprilli R, Frieri G, Latella G, et al. Faecal excretion of bicarbonate in ulcerative colitis. Digestion. 1986;35:136-142.
60. Schilli R, Breuer RI, Klein F, et al. Comparison of the composition of faecal fluid in Crohn's disease and ulcerative colitis. Gut. 1982;23:326-332.
61. Yang H, Jiang W, Furth EE, et al. Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea. Am J Physiol. 1998;275:G1445-G1453.
62. Haila S, Saarialho-Kere U, Karjalainen-Lindsberg ML, et al. The congenital chloride diarrhea gene is expressed in seminal vesicle, sweat gland, inflammatory colon epithelium, and in some dysplastic colon cells. His-tochem Cell Biol. 2000;113:279-286.
63. Xiao F, Juric M, Li J, et al. Loss of downregulated in adenoma (DRA) impairs mucosal HCO3(-) secretion in murine ileocolonic inflammation. Inflamm Bowel Dis. 2012;18:101-111.
64. Singh V, Kumar A, Raheja G, et al. Lactobacillus acidophilus attenuates downregulation of DRA function and expression in inflammatory models. Am J Physiol Gastrointest Liver Physiol. 2014;307:G623-G631.
65. Xu L, Xiao F, He J, et al. Lysophosphatidic acid increases SLC26A3 expression in inflamed intestine and reduces diarrheal severity in C57BL/6 mice with dextran-sodium-sulfate-induced colitis. Chin Med J (Engl). 2014;127:1737-1743.
66. Saksena S, Singla A, Goyal S, et al. Mechanisms of transcriptional modulation of the human anion exchanger SLC26A3 gene expression by IFN-{gamma}. Am J Physiol Gastrointest Liver Physiol. 2010;298: G159-G166.
67. Kumar A, Gujral T, Gill RK, et al. TNF Inhibits SLC26A3 expression via activation of NF-KB pathway. Gastroenterology. 2014;146(suppl 1): S650.
68. Saksena S, Gill RK, Tyagi S, et al. Role of Fyn and PI3K in H2O2-induced inhibition of apical Cl-/OH-exchange activity in human intestinal epithelial cells. Biochem J. 2008;416:99-108.
69. Asano K, Matsushita T, Umeno J, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet. 2009;41:1325-1329.
70. Xiao F, Yu Q, Li J, et al. Slc26a3 deficiency is associated with loss of colonic HCO3 (-) secretion, absence of a firm mucus layer and barrier impairment in mice. Acta Physiol (Oxf). 2014;211:161-175.
71. Serafini EP, Kirk AP, Chambers TJ. Rate and pattern of epithelial cell proliferation in ulcerative colitis. Gut. 1981;22:648-652.
72. Johansson ME, Gustafsson JK, Holmen-Larsson J, et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut. 2014; 63:281-291.
73. Zhu H, Li YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood). 2012;237:474-480.
74. Kolios G, Valatas V, Ward SG. Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzle. Immunology. 2004; 113:427-437.
75. Saksena S, Gill RK, Syed IA, et al. Modulation of Cl-/OH-exchange activity in Caco-2 cells by nitric oxide. Am J Physiol Gastrointest Liver Physiol. 2002;283:G626-G633.