Influence of Collagen and TGF-$\beta$I Gene Expression and Hepatic Fibrogenesis by Iron Overload in Rat

철 과잉투여가 흰쥐의 Hepatic Fibrogenesis와 Collagen 및 TGF-$\beta$I 유전자 발현에 미치는 영향

  • 양영목 (건국대학교 의과대학 의예과) ;
  • 박종환 (건국대학교 의과대학 의예과) ;
  • 이현영 (건국대학교 의과대학 의예과) ;
  • 정연희 (건국대학교 의과대학 의예과) ;
  • 김해영 (경희대학교 생명과학부 및 식물대사 연구센터)
  • Published : 2001.04.01

Abstract

Iron excess is known to affect long-term iron accumulation and tissue change such as fibrosis in liver. To determine the changes of expression level of genes associated with fibrosis by short-term iron exposure, we measured liver mRNA levels by reverse transcription polymerase chain reaction (RT-PCR) in rats fed dietary carbonyl iron (3%, wt/wt) for 9 weeks. The results showed that the expression of the collagen (I, III) and transforming growth factor (TGF)-$\beta$I mRNAs was enhanced in high-dose iron treated rat, compared to normal-dose iron treated rat. An electron microscopy study revealed that excess iron caused increase of collagen fibrils in liver. The cell shapes and compositions of hepatocytes and extracellular matrix(ECM) in liver were changed by the iron-treatment. Also, necrosised hepatocytes were broadly seen in ECM. Taken together, we suggest that iron overload affects changes of collagen and TGF-$\beta$I gene expression and these changes are associated with liver fibrogenesis.

Keywords

References

  1. Annu.Rev.Nutr v.6 Biochemical basic for the manifestations of iron deficiency Dallman,P.R
  2. J.Nutr. v.128 Iron regulatory proteins. iron responsive elements and iron homeostasis Eisenstein,R.S;Blemings,K.P
  3. Proc.Natl.Acad.Sci. v.93 Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron,nitric oxide, and oxidative stress Hentze,M.W;Kuhn,L.C
  4. Sencondary iron overload. In Iron metabolism in health and disease Pippard,M.J;Brock,J.H(ed);Halliday,J.W(ed);Pippard,M.J(ed);Powell,L.W(eds)
  5. Blood v.75 Manipulation of cellular iron metabolism for modulating normal and malignant cell proliferation: achievements and prospects Mario.C;Gaetano,B;Laura,D;Paolo,A
  6. J.Biol.Chem. v.267 The iron-responsive element binding protein Yang,Y;Evette,R;Elizabeth,A.L
  7. Chem.Biol.Interact v.70 Hepatic injury in chronic iron overload role of lipid peroxidation Bacon,B.R;Britton,R.S
  8. Hepatology v.29 Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells differential effects on signal transduction pathways Gianluca,S.B;Francesco,R;Antonio,D.S;Alessandro,C;Luca,M
  9. Gastroenterology v.76 Collagen type in normal and cirrhotic liver Rojkind,M;Giambrone,M.A;Biempica,L
  10. Semin Liver Dis. v.10 Structural of the extracellular matrix in normal and fibrotic liver: collagen and glycoproteins Schuppan,D
  11. Lab.Invest v.73 Critical role of extracellular matrix on induction by phenobarbital of cytochrome P450 2B1/2 in primary cultures of adult rat hepatocytes Brown,S.E;Guzelian,C.P;Schuetz,E;Quattrochi,L.C;Kleinman,H.K;Guzelian,P.S
  12. Eur.J.Biochem. v.213 Crude liver membrane fractions and extracellular matrix components as substrata regulate differentially the preservation and inducibility of cytochrome P-450 isoenzymes in cultured rat hepatocytes Saad,B;Scholl,F.A;Thomas,H;Schawalder,H;Streit,V;Waechiter,F;Maier,P
  13. N.Engl.J.Med v.328 Seminars in medicine of the Beth Israel Hospita, Boston. The Cellular basis of hepatic fibrosis. Mechanisms and treatment strategies Friedman,S.L
  14. Ratinoid(vitamin A) metabolism and the liver In The Liver Biology and pathbiology v.9 Blaner,W.S;Arias,I.M(ed);Boyer,J.L(ed);Fausto,N(eds)
  15. Hepatology v.20 Collagen-acetaldehyde adducts in alcoholic and nonalcoholic liver diseases Svegliati-Baroni,G;Baraona,E;Rosman,A.S;Lieber,C.S
  16. J.Biol.Chem v.262 Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta Ignotz,R.A;Endo,T;Massague,J
  17. J.Biol.Chem. v.261 Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix Ignotz,R.A;Massague,J
  18. J.Clin Invest v.79 Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts Raghow,R;Postlehwaite,A.E;Keski-Oja;J.Moses,H.L;Kang,A.H
  19. Anal.Biochem. v.162 Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Chomezynski,P;Sacchi,N
  20. J.Biochem.Mol.Biol v.33 Screening of differentially expressed genes by desferi-oxamine or ferric ammonium citrate treatment in HepG2 cells Park,J.H;Lee,H.Y;Roh,S.C;Kim,H.Y;Yang,Y.M
  21. Hepatology v.27 Fibrogenic effect of oxidative stress on rat hapatic stellate cells Svegliati-Baroni.G;D'Ambrosio,L;Ferritti,G;Casini,A;DiSario,A;Salzano.R;Ridolft,F
  22. J.Biol.Chem. v.264 Stimulation of collagen gene expression by ascorbic acid in cultured human fibroblasts. A role for lipid peroxidation? Chojkier,M;Houglum,K;Solls-Herruzo,J;Brenner,D.A
  23. Gastroenterlogy v.105 Hepatic mitochondrial energy production in rats with chronic iron load Bacon,B.R;O'Neill,R;Britton,R.S
  24. Semin Liver Dis v.4 Genetic hemochromatosis Bassett,M.L;Halliday,J.W;Powell,L.W
  25. Hemochromatosis iron metabolism and the iron overload syndromes. In Hepatology: a textbook of liver disease Tavill,A.S;Bacon,B.R;Zakim,D(ed);Boyer,T.D(eds.)
  26. Endocrinology v.137 Type I procollagen production and cell proliferation in mediated by transforming growth factor-beta in a model of hepatic fibrosis Eghbali-Fatourechi,G;Sieck,G.C;Prakash,Y.S;Maercklein,P;Gores,G.J;Fitzpatrick,L.A
  27. Int.J.Biochem.Cell Biol v.29 Tissue inhibitors of metalloproteinases in liver fibrosis Iredale,J.P
  28. Hepatogastronterology v.31 Changes of collagen types at various stages of human liver cirrhosis Murata,K;Kudo,M;Onuma,F;Motoyama,T