Home LiteratureArticle Details
PMID: 2592560 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells.

The Journal of clinical investigation ·Vol. 84 ·No. 6 ·1989-12-00 ·Pages 1786-93

Pinzani M, Gesualdo L, Sabbah GM, Abboud HE

Abstract

In vitro and in vivo studies suggest that liver fat-storing cells (FSC) may play an important role in the development of liver fibrosis. We explored the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and TGF-beta, and basic fibroblast growth factor (bFGF) on DNA synthesis and growth of rat liver FSC. PDGF, EGF, TGF-alpha, and bFGF induced a dose-dependent increase in DNA synthesis with a peak effect at 24 h. PDGF produced the most striking effect with a maximum 18-fold increase over control. EGF, TGF-alpha, and bFGF elicited a maximum three- to fourfold increase in DNA synthesis. Analysis of growth curves revealed a similar pattern of potency of the growth factors. TGF-beta did not affect DNA synthesis of FSC; however, TGF-beta markedly potentiated the stimulatory effects of both EGF and PDGF. FSC showed high specific binding of 125I-PDGF and Scatchard analysis revealed high affinity receptors with an apparent Kd of 2.3 x 10(-10) M. Our data suggest that PDGF is a key mitogen for FSC and that the coordinate release of other growth factors together with PDGF by inflammatory cells represents a potent potential stimulus for FSC proliferation in conditions of chronic self-perpetuating liver inflammation.

MeSH Terms
Animals DNA/biosynthesis Drug Synergism Epidermal Growth Factor/pharmacology Fibroblast Growth Factors/pharmacology Lipid Metabolism Liver/cytology,metabolism Male Mitogens/pharmacology Platelet-Derived Growth Factor/pharmacology Rats Rats, Inbred Strains Transforming Growth Factors/pharmacology
Chemicals
Mitogens Platelet-Derived Growth Factor Fibroblast Growth Factors Epidermal Growth Factor Transforming Growth Factors DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pinzani M
Department of Medicine and Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Gesualdo L
Sabbah G M
Abboud H E
References (42)
42 references, click to expand
  1. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia.
    Proc Natl Acad Sci U S A. 1981 Jun;78(6):3664-8 PMID: 6943569
  2. Dual control of cell growth by somatomedins and platelet-derived growth factor.
    Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279-83 PMID: 312500
  3. Platelet-derived growth factor. II. Specific binding to cultured cells.
    J Biol Chem. 1982 May 10;257(9):5161-71 PMID: 6279659
  4. Correlation between Ito cells and fibrogenesis in an experimental model of hepatic fibrosis. A sequential stereological study.
    Liver. 1983 Feb;3(1):58-63 PMID: 6855489
  5. Alcoholic liver injury in baboons: transformation of lipocytes to transitional cells.
    Gastroenterology. 1984 Jul;87(1):188-200 PMID: 6539267
  6. Purified rat liver fat-storing cells in culture divide and contain collagen.
    Hepatology. 1984 May-Jun;4(3):392-403 PMID: 6373550
  7. Cellular transformation by coordinated action of three peptide growth factors from human platelets.
    Nature. 1984 Jun 28-Jul 4;309(5971):804-6 PMID: 6330562
  8. Immunocytochemical detection of desmin in fat-storing cells (Ito cells).
    Hepatology. 1984 Jul-Aug;4(4):709-14 PMID: 6204917
  9. Platelet-derived growth factor. Structure, function, and roles in normal and transformed cells.
    J Clin Invest. 1984 Sep;74(3):669-76 PMID: 6088582
  10. Induction of collagenase secretion in human fibroblast cultures by growth promoting factors.
    J Biol Chem. 1985 May 10;260(9):5213-6 PMID: 2985581
  11. Stimulation of in vitro human skin collagenase expression by platelet-derived growth factor.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4132-6 PMID: 2987965
  12. Biphasic effects of type beta transforming growth factor on epidermal growth factor receptors in NRK fibroblasts. Functional consequences for epidermal growth factor-stimulated mitosis.
    J Biol Chem. 1985 Aug 15;260(17):9613-7 PMID: 2991254
  13. Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells.
    J Biol Chem. 1985 Nov 5;260(25):13560-5 PMID: 2997171
  14. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF.
    Cell. 1985 Nov;43(1):277-86 PMID: 2416458
  15. Hepatic lipocytes: the principal collagen-producing cells of normal rat liver.
    Proc Natl Acad Sci U S A. 1985 Dec;82(24):8681-5 PMID: 3909149
  16. Transient expression of type IV collagenolytic metalloproteinase by human mononuclear phagocytes.
    J Biol Chem. 1986 Feb 15;261(5):2369-75 PMID: 3003112
  17. Cell types involved in collagen and fibronectin production in normal and fibrotic human liver.
    Hepatology. 1986 Mar-Apr;6(2):225-34 PMID: 3514407
  18. The biology of platelet-derived growth factor.
    Cell. 1986 Jul 18;46(2):155-69 PMID: 3013421
  19. Peptide growth factors and inflammation, tissue repair, and cancer.
    J Clin Invest. 1986 Aug;78(2):329-32 PMID: 3525608
  20. Collagen production by rat liver fat-storing cells in primary culture.
    Exp Cell Biol. 1986;54(4):183-92 PMID: 3536634
  21. Isolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan.
    Anal Biochem. 1987 Feb 15;161(1):207-18 PMID: 3578783
  22. Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation.
    Proc Natl Acad Sci U S A. 1988 Mar;85(5):1539-43 PMID: 3422749
  23. Immunolocalization of laminin in normal rat liver and biosynthesis of laminin by hepatic lipocytes in primary culture.
    Gastroenterology. 1988 Apr;94(4):1053-62 PMID: 3278941
  24. Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta.
    Endocrinology. 1988 Jul;123(1):98-105 PMID: 2838270
  25. Formation of extracellular matrix in normal rat liver: lipocytes as a major source of proteoglycan.
    Gastroenterology. 1988 Aug;95(2):441-7 PMID: 3292336
  26. Desmin distinguishes cultured fat-storing cells from myofibroblasts, smooth muscle cells and fibroblasts in the rat.
    J Hepatol. 1988 Jun;6(3):267-76 PMID: 3292636
  27. Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer.
    J Clin Invest. 1988 Aug;82(2):450-9 PMID: 3042806
  28. Lipocytes and transitional cells in alcoholic liver disease: a morphometric study.
    Hepatology. 1988 Sep-Oct;8(5):1027-33 PMID: 3417223
  29. Mesangial cells express PDGF mRNAs and proliferate in response to PDGF.
    Am J Physiol. 1988 Oct;255(4 Pt 2):F674-84 PMID: 2845810
  30. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA.
    Science. 1989 Jan 20;243(4889):393-6 PMID: 2783498
  31. Sera and conditioned media contain different isoforms of platelet-derived growth factor (PDGF) which bind to different classes of PDGF receptor.
    J Biol Chem. 1989 Feb 15;264(5):2502-8 PMID: 2536714
  32. Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558-62 PMID: 2922399
  33. Differential effects of interleukin-1 alpha, tumor necrosis factor alpha, and transforming growth factor beta 1 on cell proliferation and collagen formation by cultured fat-storing cells.
    Liver. 1989 Apr;9(2):71-8 PMID: 2785237
  34. Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta.
    J Biol Chem. 1989 May 15;264(14):8120-5 PMID: 2542264
  35. Maintenance of differentiated phenotype of cultured rat hepatic lipocytes by basement membrane matrix.
    J Biol Chem. 1989 Jun 25;264(18):10756-62 PMID: 2732246
  36. In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells.
    Hepatology. 1989 Jul;10(1):84-92 PMID: 2737606
  37. Hepatic fibrosis. Correlation of biochemical and morphologic investigations.
    Am J Med. 1970 Nov;49:707-21 PMID: 4924592
  38. The role of perisinusoidal cells in hepatic fibrogenesis. An electron microscopic study of acute carbon tetrachloride liver injury.
    Lab Invest. 1972 Apr;26(4):429-40 PMID: 4336540
  39. Observations on the fine structure and peroxidase cytochemistry of normal rat liver Kupffer cells.
    J Ultrastruct Res. 1974 Mar;46(3):393-426 PMID: 4363811
  40. Vitamin A-containing lipocytes and formation of type III collagen in liver injury.
    Proc Natl Acad Sci U S A. 1976 Oct;73(10):3719-22 PMID: 1068482
  41. Autoradiography.
    Methods Enzymol. 1979;58:279-92 PMID: 423767
  42. Demonstration of an antibody against platelet-derived growth factor.
    Exp Cell Res. 1981 Dec;136(2):255-61 PMID: 6171440
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114363
Published
1989-12-00
Pages
1786-93
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC304056
Subset
IM
Grants
NIDDK NIH HHS · DK-33665 · United States
External Links
PubMed source DOI: 10.1172/JCI114363 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2