Journal of Neurogastroenterology and Motility

The Korean Society of Neurogastroenterology and Motility (대한소화기 기능성질환 운동학회)
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Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex

  • Lee, Ju Yup (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Kim, Nayoung (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Park, Ji Hyun (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Nam, Ryoung Hee (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Lee, Sun Min (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Song, Chin-Hee (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Kim, Geun (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Na, Hee Young (Department of Pathology, Seoul National University Bundang Hospital) ;
  • Choi, Yoon Jin (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Kim, Jin Joo (Department of Internal Medicine, Gyeongsang National University Changwon Hospital) ;
  • Lee, Dong Ho (Department of Internal Medicine, Seoul National University Bundang Hospital)
  • Received : 2019.05.08
  • Accepted : 2019.09.27
  • Published : 2020.01.31
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Abstract

Background/Aims Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex. Methods From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay. Results TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001). Conclusion Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.

Keywords

References

  1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006;130:1480-1491. https://doi.org/10.1053/j.gastro.2005.11.061
  2. Oshima T, Miwa H. Gastrointestinal mucosal barrier function and diseases. J Gastroenterol 2016;51:768-778. https://doi.org/10.1007/s00535-016-1207-z
  3. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 2012;10:712-721, e4. https://doi.org/10.1016/j.cgh.2012.02.029
  4. Kim YS, Kim N. Sex and gender differences in irritable bowel syndrome. J Neurogastroenterol Motil 2018;24:544-558. https://doi.org/10.5056/jnm18082
  5. Houghton LA, Heitkemper M, Crowell M, et al. Age, gender and women's health and the patient. Gastroenterology 2016;150:1332-1343, e4. https://doi.org/10.1053/j.gastro.2016.02.017
  6. Meleine M, Matricon J. Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones. World J Gastroenterol 2014;20:6725-6743. https://doi.org/10.3748/wjg.v20.i22.6725
  7. Lee JY, Kim N, Kim YS, et al. Repeated water avoidance stress alters mucosal mast cell counts, interleukin-1beta levels with sex differences in the distal colon of Wistar rats. J Neurogastroenterol Motil 2016;22:694-704. https://doi.org/10.5056/jnm16007
  8. Lee JY, Kim N, Nam RH, et al. Probiotics reduce repeated water avoidance stress-induced colonic microinflammation in Wistar rats in a sexspecific manner. PLoS One 2017;12:e0188992. https://doi.org/10.1371/journal.pone.0188992
  9. Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology 2002;123:1686-1701. https://doi.org/10.1053/gast.2002.36603
  10. Peters SA, Edogawa S, Sundt WJ, et al. Constipation-predominant irritable bowel syndrome females have normal colonic barrier and secretory function. Am J Gastroenterol 2017;112:913-923. https://doi.org/10.1038/ajg.2017.48
  11. Barbara G, Cremon C, Carini G, et al. The immune system in irritable bowel syndrome. J Neurogastroenterol Motil 2011;17:349-359. https://doi.org/10.5056/jnm.2011.17.4.349
  12. Yu YB, Zuo XL, Zhao QJ, et al. Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome. Gut 2012;61:685-694. https://doi.org/10.1136/gutjnl-2011-300265
  13. Akbar A, Yiangou Y, Facer P, Walters JR, Anand P, Ghosh S. Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut 2008;57:923-929. https://doi.org/10.1136/gut.2007.138982
  14. Bertiaux-Vandaele N, Youmba SB, Belmonte L, et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 2011;106:2165-2173. https://doi.org/10.1038/ajg.2011.257
  15. Coeffier M, Gloro R, Boukhettala N, et al. Increased proteasomemediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010;105:1181-1188. https://doi.org/10.1038/ajg.2009.700
  16. Macsharry J, O'Mahony L, Fanning A, et al. Mucosal cytokine imbalance in irritable bowel syndrome. Scand J Gastroenterol 2008;43:1467-1476. https://doi.org/10.1080/00365520802276127
  17. Matricon J, Meleine M, Gelot A, et al. Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther 2012;36:1009-1031. https://doi.org/10.1111/apt.12080
  18. Choi YJ, Hwang SW, Kim N, Park JH, Oh JC, Lee DH. Association between SLC6A4 serotonin transporter gene lainked polymorphic region and ADRA2A -1291C>G and irritable bowel syndrome in Korea. J Neurogastroenterol Motil 2014;20:388-399. https://doi.org/10.5056/jnm14020
  19. Choi YJ, Kim N, Yoon H, et al. Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses. J Gastroenterol Hepatol 2017;32:1553-1561. https://doi.org/10.1111/jgh.13756
  20. Kim JJ, Kim N, Choi YJ, Kim JS, Jung HC. Increased TRPV1 and PAR2 mRNA expression levels are associated only with the esophageal reflux symptoms, but not with the extraesophageal reflux symptoms. Medicine (Baltimore) 2016;95:e4387. https://doi.org/10.1097/MD.0000000000004387
  21. Kim JJ, Kim N, Park JH, et al. Comparison of tight junction protein-related gene mRNA expression levels between male and female gastroesophageal reflux disease patients. Gut Liver 2018;12:411-419. https://doi.org/10.5009/gnl17419
  22. Song CH, Kim N, Sohn SH, et al. Effects of 17beta-estradiol on colonic permeability and inflammation in an azoxymethane/dextran sulfate sodium-induced colitis mouse model. Gut Liver 2018;12:682-693. https://doi.org/10.5009/gnl18221
  23. Ma J, Altomare A, Guarino M, et al. HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2012;303:G635-G645. https://doi.org/10.1152/ajpgi.00097.2012
  24. Yoshida N, Kuroda M, Suzuki T, et al. Role of nociceptors/neuropeptides in the pathogenesis of visceral hypersensitivity of nonerosive reflux disease. Dig Dis Sci 2013;58:2237-2243. https://doi.org/10.1007/s10620-012-2337-7
  25. Son HJ, Sohn SH, Kim N, et al. Effect of estradiol in an azoxymethane/dextran sulfate sodium-treated mouse model of colorectal cancer: implication for sex difference in colorectal cancer development. Cancer Res Treat 2019;51:632-648. https://doi.org/10.4143/crt.2018.060
  26. Choi YJ, Kim N, Kim J, Lee DH, Park JH, Jung HC. Upregulation of vanilloid receptor-1 in functional dyspepsia with or without Helicobacter pylori infection. Medicine (Baltimore) 2016;95:e3410. https://doi.org/10.1097/MD.0000000000003410
  27. Xu XJ, Zhang YL, Liu L, Pan L, Yao SK. Increased expression of nerve growth factor correlates with visceral hypersensitivity and impaired gut barrier function in diarrhoea-predominant irritable bowel syndrome: a preliminary explorative study. Aliment Pharmacol Ther 2017;45:100-114. https://doi.org/10.1111/apt.13848
  28. Dothel G, Barbaro MR, Boudin H, et al. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 2015;148:1002-1011, e4. https://doi.org/10.1053/j.gastro.2015.01.042
  29. Steinkamp M, Geerling I, Seufferlein T, et al. Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. Gastroenterology 2003;124:1748-1757. https://doi.org/10.1016/S0016-5085(03)00404-9
  30. Shieh KR, Yi CH, Liu TT, et al. Evidence for neurotrophic factors associating with TRPV1 gene expression in the inflamed human esophagus. Neurogastroenterol Motil 2010;22:971-977, e252. https://doi.org/10.1111/j.1365-2982.2010.01530.x
  31. Lee SH. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res 2015;13:11-18. https://doi.org/10.5217/ir.2015.13.1.11
  32. Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 2000;279:G851-G857. https://doi.org/10.1152/ajpgi.2000.279.5.G851
  33. Zeisel MB, Dhawan P, Baumert TF. Tight junction proteins in gastrointestinal and liver disease. Gut 2019;68:547-561. https://doi.org/10.1136/gutjnl-2018-316906
  34. Van Itallie CM, Anderson JM. Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol 2014;36:157-165. https://doi.org/10.1016/j.semcdb.2014.08.011
  35. Piche T, Barbara G, Aubert P, et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009;58:196-201. https://doi.org/10.1136/gut.2007.140806
  36. Dunlop SP, Jenkins D, Neal KR, Spiller RC. Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology 2003;125:1651-1659. https://doi.org/10.1053/j.gastro.2003.09.028
  37. Gwee KA, Collins SM, Read NW, et al. Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut 2003;52:523-526. https://doi.org/10.1136/gut.52.4.523
  38. Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology 2006;130:304-311. https://doi.org/10.1053/j.gastro.2005.11.033
  39. Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology 2007;132:913-920. https://doi.org/10.1053/j.gastro.2007.01.046
  40. Chang L, Adeyemo M, Karagiannides I, et al. Serum and colonic mucosal immune markers in irritable bowel syndrome. Am J Gastroenterol 2012;107:262-272. https://doi.org/10.1038/ajg.2011.423

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