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Glial Cell Line-Derived Neurotrophic Factor, S-100 Protein and Synaptophysin Expression in Biliary Atresia Gallbladder Tissue

  • Gurunluoglu, Semra (Department of Pathology Malatya Education and Research Hospital, Pathology Laboratory) ;
  • Ceran, Canan (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Gurunluoglu, Kubilay (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Kocbiyik, Alper (Department of Pathology, Istanbul Bakirkoy Dr Sadi Konuk Education and Research Hospital, Pathology Laboratory) ;
  • Gul, Mehmet (Department of Histology and Embryology, Faculty of Medicine, Inonu University) ;
  • Yildiz, Turan (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Bag, Harika Gozukara (Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University) ;
  • Gul, Semir (Department of Histology and Embryology, Faculty of Medicine, Inonu University) ;
  • Tasci, Aytac (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Bayrakci, Ercan (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Akpinar, Necmettin (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Cin, Ecem Serbest (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Ates, Hasan (Department of Pediatric Surgery, Faculty of Medicine, Inonu University) ;
  • Demircan, Mehmet (Department of Pediatric Surgery, Faculty of Medicine, Inonu University)
  • Received : 2020.08.07
  • Accepted : 2020.10.20
  • Published : 2021.03.15

Abstract

Purpose: Biliary atresia (BA) is a disease that manifests as jaundice after birth and leads to progressive destruction of the ductal system in the liver. The aim of this study was to investigate histopathological changes and immunohistochemically examine the expression of glial cell line-derived neurotrophic factor (GDNF), synaptophysin, and S-100 protein in the gallbladder of BA patients. Methods: The study included a BA group of 29 patients and a control group of 41 children with cholecystectomy. Gallbladder tissue removed during surgery was obtained and examined immunohistochemically and histopathologically. Tissue samples of both groups were immunohistochemically assessed in terms of GDNF, S-100 protein, and synaptophysin expression. Expression was classified as present or absent. Inflammatory activity assessment with hematoxylin and eosin staining and fibrosis assessment with Masson's trichrome staining were performed for tissue sample sections of both groups. Results: Ganglion cells were not present in gallbladder tissue samples of the BA group. Immunohistochemically, GDNF, synaptophysin, and S-100 expression was not detected in the BA group. Histopathological examination revealed more frequent fibrosis and slightly higher inflammatory activity in the BA than in the control group. Conclusion: We speculate that GDNF expression will no longer continue in this region, when the damage caused by inflammation of the extrahepatic bile ducts reaches a critical threshold. The study's findings may represent a missing link in the chain of events forming the etiology of BA and may be helpful in its diagnosis.

Keywords

References

  1. Altman RP, Buchmiller TL. The jaundiced infant: biliary atresia. In: Grosfeld JL, O'Neill JA Jr, Fonkalsrud EW, Coran AG, eds. Pediatric surgery. 6th ed. Philadelphia: Elsevier, 2006:1603-19.
  2. Mezina A, Karpen SJ. Genetic contributors and modifiers of biliary atresia. Dig Dis 2015;33:408-14. https://doi.org/10.1159/000371694
  3. Morecki R, Glaser JH, Cho S, Balistreri WF, Horwitz MS. Biliary atresia and reovirus type 3 infection. N Engl J Med 1982;307:481-4. https://doi.org/10.1056/NEJM198208193070806
  4. Rauschenfels S, Krassmann M, Al-Masri AN, Verhagen W, Leonhardt J, Kuebler JF, et al. Incidence of hepatotropic viruses in biliary atresia. Eur J Pediatr 2009;168:469-76. https://doi.org/10.1007/s00431-008-0774-2
  5. Petersen C, Davenport M. Aetiology of biliary atresia: what is actually known? Orphanet J Rare Dis 2013;8:128. https://doi.org/10.1186/1750-1172-8-128
  6. Schafer KH, Mestres P. The GDNF-induced neurite outgrowth and neuronal survival in dissociated myenteric plexus cultures of the rat small intestine decreases postnatally. Exp Brain Res 1999;125:447-52. https://doi.org/10.1007/s002210050702
  7. Martucciello G, Thompson H, Mazzola C, Morando A, Bertagnon M, Negri F, et al. GDNF deficit in Hirschsprung's disease. J Pediatr Surg 1998;33:99-102. https://doi.org/10.1016/S0022-3468(98)90371-2
  8. Yadav L, Babu MK, Das K, Mohanty S, Divya P, Shankar G, et al. Role of synaptophysin in the intraoperative assessment of quadrantic innervation of the proximal doughnut in Hirschsprung disease. Natl Med J India 2017;30:187-92. https://doi.org/10.4103/0970-258X.218669
  9. Sheppard MN, Kurian SS, Henzen-Logmans SC, Michetti F, Cocchia D, Cole P, et al. Neurone-specific enolase and S-100: new markers for delineating the innervation of the respiratory tract in man and other mammals. Thorax 1983;38:333-40. https://doi.org/10.1136/thx.38.5.333
  10. Barcia JJ. Histologic analysis of chronic inflammatory patterns in the gallbladder: diagnostic criteria for reporting cholecystitis. Ann Diagn Pathol 2003;7:147-53. https://doi.org/10.1016/S1092-9134(03)00011-X
  11. Landing BH. Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst--the concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 1974;6:113-39. PUBMED
  12. Nakashima T, Hayashi T, Tomoeda S, Yoshino M, Mizuno T. Reovirus type-2-triggered autoimmune cholangitis in extrahepatic bile ducts of weanling DBA/1J mice. Pediatr Res 2014;75:29-37. https://doi.org/10.1038/pr.2013.170
  13. Lakshminarayanan B, Davenport M. Biliary atresia: a comprehensive review. J Autoimmun 2016;73:1-9. https://doi.org/10.1016/j.jaut.2016.06.005
  14. Mack CL, Sokol RJ. Unraveling the pathogenesis and etiology of biliary atresia. Pediatr Res 2005;57(5 Pt 2):87R-94R. https://doi.org/10.1203/01.pdr.0000159569.57354.47
  15. Nakamura K, Tanoue A. Etiology of biliary atresia as a developmental anomaly: recent advances. J Hepatobiliary Pancreat Sci 2013;20:459-64. https://doi.org/10.1007/s00534-013-0604-4
  16. Zhao D, Long XD, Xia Q. Recent advances in etiology of biliary atresia. Clin Pediatr (Phila) 2015;54:723-31. https://doi.org/10.1177/0009922814548841
  17. Lachaux A, Descos B, Plauchu H, Wright C, Louis D, Raveau J, et al. Familial extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 1988;7:280-3. https://doi.org/10.1097/00005176-198803000-00020
  18. Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet 2009;374:1704-13. https://doi.org/10.1016/S0140-6736(09)60946-6
  19. Cui S, Leyva-Vega M, Tsai EA, EauClaire SF, Glessner JT, Hakonarson H, et al. Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility gene. Gastroenterology 2013;144:1107-15.e3. https://doi.org/10.1053/j.gastro.2013.01.022
  20. Davit-Spraul A, Baussan C, Hermeziu B, Bernard O, Jacquemin E. CFC1 gene involvement in biliary atresia with polysplenia syndrome. J Pediatr Gastroenterol Nutr 2008;46:111-2. https://doi.org/10.1097/01.mpg.0000304465.60788.f4
  21. Arikan C, Berdeli A, Ozgenc F, Tumgor G, Yagci RV, Aydogdu S. Positive association of macrophage migration inhibitory factor gene-173G/C polymorphism with biliary atresia. J Pediatr Gastroenterol Nutr 2006;42:77-82. https://doi.org/10.1097/01.mpg.0000192247.55583.fa
  22. Kohsaka T, Yuan ZR, Guo SX, Tagawa M, Nakamura A, Nakano M, et al. The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresia. Hepatology 2002;36(4 Pt 1):904-12. https://doi.org/10.1053/jhep.2002.35820
  23. Teitelbaum DH, Coran AG. Hirschsprung's disease and related neuromuscular disorders of the intestine. In: Grosfeld JL, O'Neill JA Jr, Fonkalsrud EW, Coran AG, eds. Pediatric surgery. 6th ed. Philadelphia: Elsevier, 2006:1514-59.
  24. Clarkson ED, Zawada WM, Freed CR. GDNF improves survival and reduces apoptosis in human embryonic dopaminergic neurons in vitro. Cell Tissue Res 1997;289:207-10. https://doi.org/10.1007/s004410050867
  25. Han TY, Lourenssen S, Miller KG, Blennerhassett MG. Intestinal smooth muscle phenotype determines enteric neuronal survival via GDNF expression. Neuroscience 2015;290:357-68. https://doi.org/10.1016/j.neuroscience.2015.01.056
  26. Meir M, Burkard N, Ungewiß H, Diefenbacher M, Flemming S, Kannapin F, et al. Neurotrophic factor GDNF regulates intestinal barrier function in inflammatory bowel disease. J Clin Invest 2019;129:2824-40. https://doi.org/10.1172/JCI120261
  27. Brun P, Gobbo S, Caputi V, Spagnol L, Schirato G, Pasqualin M, et al. Toll like receptor-2 regulates production of glial-derived neurotrophic factors in murine intestinal smooth muscle cells. Mol Cell Neurosci 2015;68:24-35. https://doi.org/10.1016/j.mcn.2015.03.018
  28. Meir M, Flemming S, Burkard N, Bergauer L, Metzger M, Germer CT, et al. Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro. Am J Physiol Gastrointest Liver Physiol 2015;309:G613-24. https://doi.org/10.1152/ajpgi.00357.2014
  29. Gougeon PY, Lourenssen S, Han TY, Nair DG, Ropeleski MJ, Blennerhassett MG. The pro-inflammatory cytokines IL-1β and TNFα are neurotrophic for enteric neurons. J Neurosci 2013;33:3339-51. https://doi.org/10.1523/JNEUROSCI.3564-12.2013
  30. Demirbilek S, Edali MN, Gurunluoglu K, Turkmen E, Tas E, Karaman A, et al. Glial cell line-derived neurotrophic factor and synaptophysin expression in pelviureteral junction obstruction. Urology 2006;67:400-5. https://doi.org/10.1016/j.urology.2005.08.056
  31. Xia ZQ, Ding DK, Zhang N, Wang JX, Yang HY, Zhang D. MicroRNA-211 causes ganglion cell dysplasia in congenital intestinal atresia via down-regulation of glial-derived neurotrophic factor. Neurogastroenterol Motil 2016;28:186-95. https://doi.org/10.1111/nmo.12705
  32. Grandi D, Becchi G, Guerrini R, Calo G, Morini G. Nociceptin/orphanin FQ and stress regulate synaptophysin expression in the rat fundic and colonic mucosa. Tissue Cell 2015;47:147-51. https://doi.org/10.1016/j.tice.2015.01.006
  33. Khen N, Jaubert F, Sauvat F, Fourcade L, Jan D, Martinovic J, et al. Fetal intestinal obstruction induces alteration of enteric nervous system development in human intestinal atresia. Pediatr Res 2004;56:975-80. https://doi.org/10.1203/01.PDR.0000145294.11800.71
  34. Ozguner IF, Savas C, Ozguner M, Candir O. Intestinal atresia with segmental musculature and neural defect. J Pediatr Surg 2005;40:1232-7. https://doi.org/10.1016/j.jpedsurg.2005.05.032
  35. Fano G, Biocca S, Fulle S, Mariggio MA, Belia S, Calissano P. The S-100: a protein family in search of a function. Prog Neurobiol 1995;46:71-82. https://doi.org/10.1016/0301-0082(94)00062-M
  36. Holland SK, Hessler RB, Reid-Nicholson MD, Ramalingam P, Lee JR. Utilization of peripherin and S-100 immunohistochemistry in the diagnosis of Hirschsprung disease. Mod Pathol 2010;23:1173-9. https://doi.org/10.1038/modpathol.2010.104
  37. Wang X, Yuan C, Xiang L, Li X, Zhao Z, Jin X. The clinical significance of pathological studies of congenital intestinal atresia. J Pediatr Surg 2013;48:2084-91. https://doi.org/10.1016/j.jpedsurg.2013.05.025
  38. Stelow EB, Hong SM, Frierson HF Jr. Gallbladder and extrahepatic biliary system. In: Mills SE, ed. Histology for pathologists. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012:759-76.
  39. Tixier E, Lalanne F, Just I, Galmiche JP, Neunlist M. Human mucosa/submucosa interactions during intestinal inflammation: involvement of the enteric nervous system in interleukin-8 secretion. Cell Microbiol 2005;7:1798-810. https://doi.org/10.1111/j.1462-5822.2005.00596.x