Skip to main content
Log in

Modulation of collagen synthesis by fat-storing cells, isolated from CCl4-or vitamin A-treated rats

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

In an attempt to elucidate the role of fat-storing cells (FSCs) in liver fibrosis, we investigated the collagen synthesis by FSCs freshly isolated from rats treated with CCl4, with vitamin A, and from untreated rats. FSCs from CCl4-treated rats contained a small number of lipid droplets and an abundant rough endoplasmic reticulum (RER), while those from vitamin A-treated rats showed numerous large lipid droplets and scanty RER. The population doubling times of FSCs isolated from normal, CCl4-treated, and vitamin A-treated rats were 38±4.3, 24±2.5, and 48±6.3 hr, respectively. The rate of collagen synthesis by FSCs from CCl4-treated rats was four- to sixfold enhanced, while collagen synthesis by FSCs from vitamin A-treated rats was suppressed. The ratio of collagen type I to type III produced by FSCs from CCl4 rats was enhanced as compared with control rats (94.7:5.3 vs 87.6:12.4). Therefore, FSCs can be considered to play an important role in the pathogenesis of liver fibrosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Grimaud, JA, Druguet M, Peyrol S, Chevalier O, Herbage D, El Badrawyn N: Collagen immunotyping in human liver. light and electron microscope study. J Histochem Cytochem 28:1145–1156, 1980

    Google Scholar 

  2. Voss B, Rauterberg J, Allan, Pott G: Distribution of type I and type III and of two collagenous component of basement membrane in the human liver. Pathol Res Pract 170:50–60, 1980

    Google Scholar 

  3. Hahn, E, Wick, G, Pencev D, Timpl AR: Distribution of basement membrane proteins in normal and fibrotic human liver; collagen type IV, laminin and fibronectin. Gut 21:63–71, 1980

    Google Scholar 

  4. Biempica L, Morecki R, Wu CH Giambrone MA, Rojkind M: Immunocytochemical localization of type B collagen. A component of basement membrane in human liver. Am J Pathol 98:591–602, 1980

    Google Scholar 

  5. Wisse E: Ultrastructure and function of Kupffer cells and other sinusoidal cells.In Kupffer Cells and Other Sinusoidal Cells.. E Wisse, DL Knook (eds). Amsterdam, Elsevier, 1977 pp 33–60

    Google Scholar 

  6. Guzelian PS, Qureshi GB, Diegelmann RF: Collagen synthesis by the hepatocytes.; studies in primary culture of parenchymal cells from adult rat liver. Collagen Res 1:83–93, 1981

    Google Scholar 

  7. Tseng SCG, Lee, PC, Ells PE, Bissell DM, Smuckler EA, Stern R: Collagen production by rat hepatocytes and sinusoidal cells in primary monolayer culture. Hepatology 2:13–18, 1982

    Google Scholar 

  8. Tseng SCG, Smuckler EA, Stern R: Types of collagen synthesized by normal rat liver hepatocytes in primary culture. Hepatology 3:955–963, 1983

    Google Scholar 

  9. Hata R, Ninomiya Y, Nagai Y, Tsukada Y: Biosynthesis of interstitial types of collagen by albumin-producing rat liver parenchymal cell (hepatocyte) clones in culture. Biochemistry 19:169–176, 1980

    Google Scholar 

  10. McGee JO, Patrick RS: The role of perisinusoidal cells in hepatic fibrogenesis; electron microscopic study of acute carbon tetrachloride liver injury. Lab Invest 26:429–440, 1972

    Google Scholar 

  11. Kent G, Gay S, Inoue T, Bahu R, Minick OT, Popper H: Vitamin A-containing lipocytes and formation of type III collagen in liver injury. Proc Natl Acad Sci USA 73:3719–3722, 1976

    Google Scholar 

  12. Mak K, Leo MA, Lieber CS: Alcoholic, liver injury in babbon; transformation of lipocytes to transitional cells. Gastroenterology 87:188–200, 1984

    Google Scholar 

  13. Minato Y, Hasumura Y, Takeuchi J: The role of fat-storing cells in Disse space fibrogenesis in alcoholic liver disease. Hepatology 3:559–566, 1983

    Google Scholar 

  14. Wake K: “Sternzellen” in the liver; perisinusoidal cells with special reference to storage of vitamin A. Am J Anat 132:429–462, 1971

    Google Scholar 

  15. Wanless IR: The cellular distribution of vitamin A in the liver. Liver 3:403–408, 1983

    Google Scholar 

  16. Russell RM, Morrison SA, Smith FR, Oaks EW, Carney EA: Vitamin A reversal of abnormal dark adaptation in cirrhosis. Study of effects on the plasma retinol transport system. Ann Intern Med 88:622–626, 1978

    Google Scholar 

  17. Sato M, Lieber CS: Hepatic vitamin A depletion after chronic ethanol consumption in baboons and rats. J Nutr 111:2015–2023, 1981

    Google Scholar 

  18. Leo MA, Lieber CS: Hepatic vitamin A depletion in alcoholic liver injury in men. N Engl J Med 37:597–601, 1982

    Google Scholar 

  19. Senoo H, Wake K, Kaneda K: Suppression of experimental hepatic fibrosis by administration of vitamin A.In Sinusoidal Liver Cells. DL Knook, E Wisse (eds). Amsterdam, Elsevier, 1982, pp 217–222

    Google Scholar 

  20. Seyer JM: Interstitial collagen polymorphism in rat liver with CCl4-induced cirrhosis. Biochim Biophys Acta 629: 490–498, 1980

    Google Scholar 

  21. Knook DL, Seffelaar AM, De Leeuw AM: Fat-storing cells of the rat liver; their isolation and purification. Exp Cell Res 139:468–471, 1982

    Google Scholar 

  22. De Leeuw AM, McCarthy SP, Geerts A, Knook DL: Purified rat liver fat-storing cells in culture divide and contain collagen. Hepatology 4:392–403, 1984

    Google Scholar 

  23. Peterkofsky B, Diegelmann R: Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry 10:988–994, 1971

    Google Scholar 

  24. Steinmann BU, Abe S, Martin GR: Modulation of type I and type III collagen production in normal and mutant human skin fibroblasts by cell density, prostaglandin E2 and epidermal growth factor. Collagen Rel Res 2:185–195, 1982

    Google Scholar 

  25. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685, 1970

    Google Scholar 

  26. Benjamin, IS, Than T, Ryan S, Rodger MC, McGee JO, Blumgart LH: Prolyl hydroxylase and collagen biosynthesis in rat liver following varying degrees of partial hepatectomy. Br J Exp Pathol 59:333–336 1978

    Google Scholar 

  27. Ehrinpreis MN, Giambrone MA, Rojkind M: Liver proline oxidase activity and collagen synthesis in rats with cirrhosis induced by carbon tetrachloride. Biochim Biophys Acta 629:184–193, 1980

    Google Scholar 

  28. Rojkind M, Giambrone MA, Biempica I: Collagen types in normal and cirrhotic liver. Gastroenterology 76:710–719, 1979

    Google Scholar 

  29. Seyer JM, Hutcheson ET, Kang AK: Collagen polymorphism in normal and cirrhotic human liver. J Clin Invest 59:241–248, 1972

    Google Scholar 

  30. Wu CH, Giambrone MA, Howard DJ, Rojkind M, Wu GY: The nature of the collagen in hepatic fibrosis in advanced murine schistosomiasis. Hepatology, 2:366–371, 1982

    Google Scholar 

  31. Rudolph R, McClure WJ, Woodward M: Contractile fibroblasts in chronic alcoholic cirrhosis. Gastroenterology 76: 704–709, 1979

    Google Scholar 

  32. Irle C, Kocher O, Gabbiani G: Contractibility of myofibroblasts during experimental liver cirrhosis. J Submicrosc Cytol 12:209–217, 1980

    Google Scholar 

  33. Nakano M, Worner TS, Lieber CS: Perivenular fibrosis in alcoholic liver injury; ultrastructure and histologic progression. Gastroenterology 83:777–785, 1982

    Google Scholar 

  34. Savolainen ER, Leo MA, Timple R, Lieber CS: Acetaldehyde and lactate stimulate collagen synthesis of cultured baboon liver myofibroblasts. Gastroenterology 87:777–787, 1984

    Google Scholar 

  35. Russell RM, Boyer SL, Bagheri SA, Hruben Z: Hepatic injury from chronic hypervitaminosis A resulting in portal hypertension and ascites. N Engl J Med 291:435–440, 1974

    Google Scholar 

  36. De Luca LM, Creek KE: Vitamin A and the liver.In Progress in Liver Diseases Vol VIII. H Popper, F Schaffner (eds). New York, Grune and Stratton, 1986, pp 81–98

    Google Scholar 

  37. Lieber CS, Leo MA: Interaction of alcohol and nutritional factors with hepatic fibrosis.In Progress in Liver Diseases, Vol VIII. H Popper, F Schaffner (eds) New York, Grune and Stratton, 1986, pp 253–272

    Google Scholar 

  38. Earnest DL, Brouwer A, Sim WW, Horan MA, Hendriks HFJ, De Leeuw AM, Knook DL: Hypervitaminosis A activates Kupffer cells and lowers the threshold for endotoxin liver injury.In Cells of the Hepatic Sinusoid, Vol I. A Kirn, DL Knook, E Wisse (eds). Rijswijk, The Kupffer Cell Foundation, 1986, pp 277–282

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shiratori, Y., Ichida, T., Geerts, A. et al. Modulation of collagen synthesis by fat-storing cells, isolated from CCl4-or vitamin A-treated rats. Digest Dis Sci 32, 1281–1289 (1987). https://doi.org/10.1007/BF01296379

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296379

Key Words

Navigation