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PMID: 8314838 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts.

The Journal of cell biology ·Vol. 122 ·No. 1 ·1993-07-00 ·Pages 103-11

Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G

Abstract

Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural and biochemical features of smooth muscle (SM) cells, including the presence of microfilament bundles and the expression of alpha-SM actin, the actin isoform typical of vascular SM cells. Myofibroblasts have been proposed to play a role in wound contraction and in retractile phenomena observed during fibrotic diseases. We show here that the subcutaneous administration of transforming growth factor-beta 1 (TGF beta 1) to rats results in the formation of a granulation tissue in which alpha-SM actin expressing myofibroblasts are particularly abundant. Other cytokines and growth factors, such as platelet-derived growth factor and tumor necrosis factor-alpha, despite their profibrotic activity, do not induce alpha-SM actin in myofibroblasts. In situ hybridization with an alpha-SM actin probe shows a high level of alpha-SM actin mRNA expression in myofibroblasts of TGF beta 1-induced granulation tissue. Moreover, TGF beta 1 induces alpha-SM actin protein and mRNA expression in growing and quiescent cultured fibroblasts and preincubation of culture medium containing whole blood serum with neutralizing antibodies to TGF beta 1 results in a decrease of alpha-SM actin expression by fibroblasts in replicative and non-replicative conditions. These results suggest that TGF beta 1 plays an important role in myofibroblast differentiation during wound healing and fibrocontractive diseases by regulating the expression of alpha-SM actin in these cells.

MeSH Terms
Actins/analysis,biosynthesis Animals Base Sequence Cells, Cultured Female Fibroblasts/drug effects,metabolism,ultrastructure Fluorescent Antibody Technique Humans In Situ Hybridization Microscopy, Immunoelectron Molecular Sequence Data Muscle, Smooth/metabolism Oligodeoxyribonucleotides RNA, Messenger/analysis,metabolism Rats Skin/drug effects,metabolism Transforming Growth Factor beta/pharmacology Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Actins Oligodeoxyribonucleotides RNA, Messenger Transforming Growth Factor beta Tumor Necrosis Factor-alpha
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Desmoulière A
University of Geneva, Department of Pathology, Switzerland.
Geinoz A
Gabbiani F
Gabbiani G
References (73)
73 references, click to expand
  1. Correlation between the distribution of smooth muscle or non muscle myosins and alpha-smooth muscle actin in normal and pathological soft tissues.
    Cell Motil Cytoskeleton. 1988;11(4):260-74 PMID: 3064925
  2. Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins.
    Lab Invest. 1989 Feb;60(2):275-85 PMID: 2644484
  3. Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes.
    J Histochem Cytochem. 1989 Mar;37(3):315-21 PMID: 2918221
  4. Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis.
    Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;56(1):45-9 PMID: 2907200
  5. Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung.
    Lab Invest. 1989 May;60(5):643-50 PMID: 2469858
  6. Transforming growth factor-beta activity is potentiated by heparin via dissociation of the transforming growth factor-beta/alpha 2-macroglobulin inactive complex.
    J Cell Biol. 1989 Jul;109(1):441-8 PMID: 2473082
  7. Subcutaneous perfusion of tumor necrosis factor induces local proliferation of fibroblasts, capillaries, and epidermal cells, or massive tissue necrosis.
    Am J Pathol. 1990 Jan;136(1):103-10 PMID: 1688687
  8. Interaction of immune and connective tissue cells: I. The effect of lymphokines and monokines on fibroblast growth.
    J Leukoc Biol. 1990 Apr;47(4):312-20 PMID: 2319205
  9. Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension.
    Am J Pathol. 1990 Apr;136(4):881-9 PMID: 2183626
  10. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  11. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction.
    Experientia. 1971 May 15;27(5):549-50 PMID: 5132594
  12. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  13. The functional importance of multiple actin isoforms.
    Bioessays. 1990 Jul;12(7):309-15 PMID: 2203335
  14. Smooth muscle differentiation in scleroderma fibroblastic cells.
    Am J Pathol. 1990 Sep;137(3):585-91 PMID: 1698026
  15. Mitogen response and cell cycle kinetics of Swiss 3T3 cells in defined medium: differences from human fibroblasts and effects of cell density.
    Exp Cell Res. 1990 Oct;190(2):145-50 PMID: 2209716
  16. Modulation of actin isoform expression in cultured arterial smooth muscle cells by heparin and culture conditions.
    Arterioscler Thromb. 1991 Mar-Apr;11(2):244-53 PMID: 1998643
  17. Differentiation requires continuous regulation.
    J Cell Biol. 1991 Mar;112(5):781-3 PMID: 1999456
  18. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation.
    J Clin Invest. 1991 Mar;87(3):847-58 PMID: 1671868
  19. Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds.
    Am J Pathol. 1991 Mar;138(3):629-46 PMID: 2000940
  20. Primary culture of adult mouse lung fibroblasts in serum-free medium: responses to growth factors.
    Exp Cell Res. 1991 Apr;193(2):398-404 PMID: 2004652
  21. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue.
    Immunol Today. 1991 Jan;12(1):17-23 PMID: 2015044
  22. Interactions of retinoids and transforming growth factor-beta in regulation of cell differentiation and proliferation.
    Mol Endocrinol. 1991 Jan;5(1):3-7 PMID: 2017191
  23. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers.
    Am J Pathol. 1991 May;138(5):1233-42 PMID: 2024709
  24. The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis.
    Am J Pathol. 1991 May;138(5):1257-65 PMID: 2024710
  25. Growth factors and wound healing: platelet-derived growth factor as a model cytokine.
    Annu Rev Med. 1991;42:567-84 PMID: 2035994
  26. Locally applied GM-CSF induces the accumulation of alpha-smooth muscle actin containing myofibroblasts.
    Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;60(2):73-82 PMID: 1675512
  27. A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat.
    Dev Biol. 1991 Dec;148(2):442-58 PMID: 1743394
  28. Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta.
    Lancet. 1992 Jan 25;339(8787):213-4 PMID: 1346175
  29. The stellate cell (Ito-cell, fat-storing cell, lipocyte, perisinusoidal cell) of the liver. New insights into pathophysiology of an intriguing cell.
    Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61(3):147-58 PMID: 1685276
  30. Growth factors as wound healing agents.
    Curr Opin Biotechnol. 1991 Dec;2(6):863-7 PMID: 1367960
  31. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair.
    Am J Pathol. 1992 Jun;140(6):1375-88 PMID: 1376557
  32. Alpha-smooth muscle actin is expressed in a subpopulation of cultured and cloned fibroblasts and is modulated by gamma-interferon.
    Exp Cell Res. 1992 Jul;201(1):64-73 PMID: 1612128
  33. Cultured aortic smooth muscle cells from newborn and adult rats show distinct cytoskeletal features.
    Differentiation. 1992 Apr;49(3):175-85 PMID: 1377654
  34. Transforming growth factor-beta in disease: the dark side of tissue repair.
    J Clin Invest. 1992 Jul;90(1):1-7 PMID: 1634602
  35. Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunologic study.
    Virchows Arch B Cell Pathol. 1976 Aug 11;21(2):133-45 PMID: 822577
  36. Coordinate control of 3T3 cell proliferation by platelet-derived growth factor and plasma components.
    Proc Natl Acad Sci U S A. 1978 Jun;75(6):2810-4 PMID: 275851
  37. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  38. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  39. Biochemistry and histology of the connective tissue of Dupuytren's disease lesions.
    Eur J Clin Invest. 1980 Feb;10(1):9-16 PMID: 6768572
  40. Permissive effect of the extracellular matrix on cell proliferation in vitro.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):4094-8 PMID: 6933458
  41. Stromal myofibroblasts in primary invasive and metastatic carcinomas. A combined immunological, light and electron microscopic study.
    Virchows Arch A Pathol Anat Histol. 1981;391(2):125-39 PMID: 7013254
  42. Localization of gold in biological tissue. A photochemical method for light and electronmicroscopy.
    Histochemistry. 1981;71(1):81-8 PMID: 6785260
  43. The matrix of human breast tumor cells is mitogenic for fibroblasts.
    Am J Pathol. 1984 Apr;115(1):109-16 PMID: 6711676
  44. Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening.
    Lab Invest. 1984 Jun;50(6):645-52 PMID: 6727297
  45. Organization of actin cytoskeleton during early endothelial regeneration in vitro.
    J Cell Sci. 1984 Mar;66:39-50 PMID: 6540272
  46. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
    Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 PMID: 6091052
  47. Cytoskeletal features of rat aortic cells during development. An electron microscopic, immunohistochemical, and biochemical study.
    Circ Res. 1985 Jun;56(6):829-38 PMID: 3891126
  48. Collagens in scar carcinoma of the lung.
    Am J Pathol. 1985 Nov;121(2):322-6 PMID: 3904470
  49. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.
    J Biol Chem. 1986 Mar 25;261(9):4337-45 PMID: 3456347
  50. The cell biology of transforming growth factor beta.
    Biochim Biophys Acta. 1990 Jun 1;1032(1):79-87 PMID: 2194569
  51. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing.
    Lab Invest. 1990 Jul;63(1):21-9 PMID: 2197503
  52. Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations.
    Lab Invest. 1990 Aug;63(2):144-61 PMID: 2116562
  53. Transforming growth factor-beta.
    Cancer Surv. 1992;12:81-103 PMID: 1638549
  54. Transforming growth factor-beta 1 is a heparin-binding protein: identification of putative heparin-binding regions and isolation of heparins with varying affinity for TGF-beta 1.
    J Cell Physiol. 1992 Aug;152(2):430-40 PMID: 1639873
  55. Transforming growth factor-beta: recent progress and new challenges.
    J Cell Biol. 1992 Dec;119(5):1017-21 PMID: 1332976
  56. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.
    Nature. 1992 Nov 26;360(6402):361-4 PMID: 1280332
  57. Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts.
    Lab Invest. 1992 Dec;67(6):716-26 PMID: 1460862
  58. Evidence for the nonmuscle nature of the "myofibroblast" of granulation tissue and hypertropic scar. An immunofluorescence study.
    Am J Pathol. 1988 Feb;130(2):252-60 PMID: 3277440
  59. Transforming growth factor type beta regulation of actin mRNA.
    J Cell Physiol. 1986 Apr;127(1):83-8 PMID: 3457016
  60. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.
    Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167-71 PMID: 2424019
  61. Opposite and selective effects of epidermal growth factor and human platelet transforming growth factor-beta on the production of secreted proteins by murine 3T3 cells and human fibroblasts.
    J Biol Chem. 1986 Aug 15;261(23):10478-81 PMID: 3488314
  62. Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta.
    J Cell Biol. 1986 Dec;103(6 Pt 1):2403-10 PMID: 3491081
  63. Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts.
    Mol Cell Biol. 1986 May;6(5):1679-86 PMID: 2431284
  64. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.
    N Engl J Med. 1986 Dec 25;315(26):1650-9 PMID: 3537791
  65. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation.
    J Cell Biol. 1986 Dec;103(6 Pt 2):2787-96 PMID: 3539945
  66. sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery.
    Proc Natl Acad Sci U S A. 1987 Feb;84(4):1099-103 PMID: 2434949
  67. Fat storing cells (FSC) of rat liver synthesize and secrete fibronectin. Comparison with hepatocytes.
    J Hepatol. 1987 Apr;4(2):190-7 PMID: 3584927
  68. The synthesis of proteoglycans in fat-storing cells of rat liver.
    Hepatology. 1987 Jul-Aug;7(4):680-7 PMID: 3111965
  69. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria.
    Science. 1987 Sep 4;237(4819):1210-2 PMID: 3306918
  70. Some recent advances in the chemistry and biology of transforming growth factor-beta.
    J Cell Biol. 1987 Sep;105(3):1039-45 PMID: 3308901
  71. Antibodies to peptide determinants in transforming growth factor beta and their applications.
    Biochemistry. 1988 Jan 26;27(2):739-46 PMID: 2450577
  72. Histogenesis of Dupuytren's disease: an immunohistochemical study of 30 cases.
    J Hand Surg Am. 1988 Jan;13(1):61-7 PMID: 3351230
  73. Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model.
    J Pediatr Surg. 1988 Jul;23(7):647-52 PMID: 3204464
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.122.1.103
Published
1993-07-00
Pages
103-11
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119614
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.122.1.103 PMC Full Text View journal details
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