Role Of Platelets-Derived Growth Factor Receptor ß and Tumor Necrosis Factor α In The Pathology Of Chronic Hepatitis C

Document Type : Original Article

Authors

1 Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University.

2 Department of, Pathology Department, Faculty of Medicine, Sohag University.

3 Department of, Tropical Medicine, and Gastroenterology Department, Faculty of Medicine,Sohag University.

Abstract

Background: Chronic liver diseases are characterized by two fundamental aspects,persistent injury and fibrosis, which are cardinal features for the continuous progression towards cirrhosis and end stage liver failure.
Objective: To study the expression of platelets derived growth factor receptor ß(PDGFR- β) and tumor necrosis factor (TNF α) in the liver and their relation to the stage and grade of chronic HCV.
Patients and Methods: Analytical cross-sectional study was conducted on fiftypatients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups according to the histological stages of chronic hepatitis C as follows, group 1 includes 40 patients in stages 0,1 and 2; whereas group 2 includes 10 patients in stage 3. All patients were then recategorized according to the grades of inflammatory activity into patients with minimal and mild inflammation (G1+G2=32 patients) and those with moderate and severe inflammation (G3 +G4=18 patients). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was evaluated for immunohistochemical expression of PDGFR- β and TNFα.
Results: The included patients were 80 % males and 20 % females. Their mean agewas 44.42±11.17 years. The mean average weighted scores (AWS) of Imunohisto-chemical expression of PDGFR- β, and TNFα were significantly higher in moderate and severe inflammation versus minimal and mild inflammation (P=0.05; 0.0001respectively). Similarly, the mean AWS of PDGFR- β, and TNFα were significantly higher in patients with stage 3 versus stages 0,1 and 2 (P=0.04; 0.0001 respectively). Conclusion: Expression of PDGFR- β, and TNFα markers were associated with progression of disease activity and fibrosis.

Keywords

References

  1. Sy  T  and  Jamal  MM  (2006): Epidemiology  of  hepatitis  C  virus  (HCV) infection. International Journal of Medical Sciences 3: 41–46
  2. NIH Consensus Statement (1997): Management of hepatitis C. 15:1–41.
  3. Popper, H., and Uenfriend, S. (1970): Hepatic fibrosis. Correlation of biochemical and morphologic investigations. Am. J. Med. 49:707–721.
  4. Albanis E, and Friedman SL (2001): Hepatic fibrosis. Pathogenesis and principles of therapy. Clin Liver Dis 5:315–334.
  5. Mannaioni PF, Di Bello MG, Masini E (1997). Platelets and inflammation: role of platelet-derived growth factor, adhesion molecules and histamine. Inflamm Res 46:4–18.
  6. Handagama PJ, George JN, Shuman MA, McEver RP, Bainton DF (1987). Incorporation of a circulating protein into megakaryocyte and PLT granules. Proc Natl Acad Sci USA 84:861–865.
  7. Italiano JE Jr, Richardson JL, Patel-Hett S, Battinelli E, ZaslavskyA, Short S, et al. (2008): Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet a granules and differentially released. Blood 111:1227–1233.
  8. Mazzucco L, Medici D, Serra M, Panizza R, Rivara G, OrecchiaS, et al. (2004): The use of autologous platelet gel to treat difficult-to-heal wounds: a pilot study. Transfusion 44:1013–1018.
  9. Nash GF, Turner LF, Scully MF, Kakkar AK (2002): Platelets and cancer. Lancet Oncol 3:425–430.
  10. Janowska-Wieczorek A, Wysoczynski M, Kijowski J, MarquezCurtis L, Machalinski B, Ratajczak J, et al. (2005): Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113:752–760.
  11. Lang PA, Contaldo C, Georgiev P, El-Badry AM, Recher M, Kurrer M, et al. (2008): Aggravation of viral hepatitis by platelet-derived serotonin. Nat Med 14:756–761.
  12. Bonner JC (2014): Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 15: 255-273.
  13. Wong L, Yamasaki G, Johnson RJ, Friedman SL (1994): Induction of PDGFR-β factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture. J Clin Invest 94: 1563–1569.
  14. Iwayama       T,     Olson     LE     (2013): Involvement            of    PDGF      in    fibrosis and scleroderma:  recent  insights  from  animal  models  and  potential  therapeutic opportunities. Curr Rheumatol Rep 15: 304.
  15. Tsochatzis E, Papatheodoridis GV and Archimandritis AJ (2006): The Evolving Role of Leptin and Adiponectin in Chronic Liver. Am J Gastroenterol 101: 2629-2640.
  16. Simpson KJ, Lukacs NW, Colletti L, Strieter RM, Kunkel SL (1997): Cytokines and the liver. J Hepatol 27:1120–1132.
  17. Zhu NL, Khoshnan A, Schneider R, Matsumoto M, Dennert G,Ware C, et al. (1998): Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor and enhances TNF-induced apoptosis. J Virol 72:3691–3697.
  18. Gonzalez–Amaro R, Garcia–Monzon G, Garcia–Buey L, Moreno–Otero R, Alonso JL, Yague E, Pivel JP, et al. (1994): Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis. J Exp Med 179: 841–848.
  19. Dumoulin FL, Leifeld L, Honecker U, Sauerbruch T, Spengler U (1999): Intrahepatic expression of interleukin-1α and tumor necrosis factor-α in chronic hepatitis C. J Infect Dis 180:1704–1708.
  20. Oyanagi Y, Takahashi T, Matsui S, Takahashi S, Boku S, TakahashiK, Furukawa K, et al. (1999): Enhanced expression of interleukin-6 in chronic hepatitis C. Liver 19:464–472.
  21. Tsukamoto H (1999): Cytokine regulation of hepatic stellate cells in liver fibrosis. Alcoholism. Clin Exp Res 23:911–916.
  22. Kasprzak A, Zabel M, Wies B, Jacek W, Agnieszka A, et al. (2004): Expression of Cytokines (TNF-α, IL-1α and IL-2) in Chronic Hepatitis C: Comparative Hybridocytochemical and Immunocytochemical Study in Children and Adult Patients. Journal of Histochemistry and Cytochemistry 52(1): 29–38.
  23. Kinnman N, Andersson U, Hultcrantz R (2000): In situ expression of transforming growth factor-beta 1–3, latent transforming growth factor-beta binding protein and tumor necrosis factor alpha in liver tissue from patients with chronic hepatitis C. ScandJ Gastroenterol 35:1294–1300.
  24. Bataller R, Gäbele E, Schoonhoven R, Morris T, Lehnert M, Yang L, Brenner DA, Rippe RA (2005): Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and necroinflammatory events in liver. AmJ Physio Gastrointest Liver Physiol 285:G642–G65.
  25. Scheuer PJ, Desmet VJ, Gerber M, Hoofnagle JH, Manns M (1994): Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19:1513–20.
  26. Moreira  R  (2007):  Hepatic  Stellate  Cells  and  Liver  Fibrosis.  Archives  of Pathology & Laboratory Medicine: November, Vol. 131, No. 11: 1728-1734. 27. Furie B (2008):. Mechanisms of thrombus formation. N Engl JMed 359:938–49.
  27. Orfila C, Lepert JC, Alric L, Carrera G, Beraud M, Vinel JP, Pipy B (1999): Expression of TNF-alpha and immunohistochemical distribution of hepatic macrophage surface markers in carbon tetrachloride-induced chronic liver injury in rats. The Histochemical Journal 31: 677-685.
  28. Kondo R, Yana H, Nakashima O, Tanikawa K, Nomura Y, and Kage M (2013): Accumulation of platelets in the liver may be an important contributory factor to thrombocytopenia and liver fibrosis in chronic hepatitis C. J Gastroenterol 48:526–534.
  29. Pinzani M, Milani S, Herbst H, DeFranco R, Grappone C, Gentilini A, et al. (2009): Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am J Pathol 148:785–800.
  30. Borkham-Kamphorst E, van Roeyen CRC, Ostendorf T, Floege J,Gressner AM, Weiskirchen R. (2007): Pro-fibrogenic potential of PDGFD in liver fibrosis. J Hepatol 46:1064–74.
  31. Kocabayoglu P, Abigale L, Youngmin A. Lee, Ana-Cristina D, Xiaochen S M, et al (2015): β-PDGF Receptor Expressed by Hepatic Stellate Cells Regulates Fibrosis in Murine Liver Injury, but Not Carcinogenesis. J Hepatol 63(1): 141– 147
  32. Ikura Y, Moromoto H, Masauki O, Histo J, Nasko I, and Masami S(1997): Expression of platelet-derived growth factor and its receptor in livers of patients with chronic liver disease. J Gastroenterol 32:496-501.
  33. Burt AD (1993): Cellular and molecular aspects of hepatic fibrosis. J pathol 170: 105-114.
  34. Pinzani M, Gesualdo L, Sabbah GM et al. (1989): Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. J Clin Invest 84: 1786-1793.

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