Abstract
Free full text
Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts
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.
Full Text
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ballardini G, Fallani M, Biagini G, Bianchi FB, Pisi E. 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):45–49. [Abstract] [Google Scholar]
- Barnard JA, Lyons RM, Moses HL. The cell biology of transforming growth factor beta. Biochim Biophys Acta. 1990 Jun 1;1032(1):79–87. [Abstract] [Google Scholar]
- Barrett TB, Benditt EP. 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):1099–1103. [Europe PMC free article] [Abstract] [Google Scholar]
- Bazin S, Le Lous M, Duance VC, Sims TJ, Bailey AJ, Gabbiani G, D'Andiran G, Pizzolato G, Browski A, Nicoletis C, et al. Biochemistry and histology of the connective tissue of Dupuytren's disease lesions. Eur J Clin Invest. 1980 Feb;10(1):9–16. [Abstract] [Google Scholar]
- Benzonana G, Skalli O, Gabbiani G. 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):260–274. [Abstract] [Google Scholar]
- Blau HM, Baltimore D. Differentiation requires continuous regulation. J Cell Biol. 1991 Mar;112(5):781–783. [Europe PMC free article] [Abstract] [Google Scholar]
- Bochaton-Piallat ML, Gabbiani F, Ropraz P, Gabbiani G. Cultured aortic smooth muscle cells from newborn and adult rats show distinct cytoskeletal features. Differentiation. 1992 Apr;49(3):175–185. [Abstract] [Google Scholar]
- Border WA, Ruoslahti E. Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest. 1992 Jul;90(1):1–7. [Europe PMC free article] [Abstract] [Google Scholar]
- Border WA, Noble NA, Yamamoto T, Harper JR, Yamaguchi Y u, Pierschbacher MD, Ruoslahti E. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature. 1992 Nov 26;360(6402):361–364. [Abstract] [Google Scholar]
- Bradford MM. 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;72:248–254. [Abstract] [Google Scholar]
- Chen YY, Rabinovitch PS. 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):145–150. [Abstract] [Google Scholar]
- Chiang CP, Nilsen-Hamilton M. 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):10478–10481. [Abstract] [Google Scholar]
- Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [Abstract] [Google Scholar]
- Danscher G. Localization of gold in biological tissue. A photochemical method for light and electronmicroscopy. Histochemistry. 1981;71(1):81–88. [Abstract] [Google Scholar]
- Darby I, Skalli O, Gabbiani G. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest. 1990 Jul;63(1):21–29. [Abstract] [Google Scholar]
- Desmoulière A, Rubbia-Brandt L, Gabbiani G. Modulation of actin isoform expression in cultured arterial smooth muscle cells by heparin and culture conditions. Arterioscler Thromb. 1991 Mar-Apr;11(2):244–253. [Abstract] [Google Scholar]
- Desmoulière A, Rubbia-Brandt L, Abdiu A, Walz T, Macieira-Coelho A, Gabbiani G. 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. [Abstract] [Google Scholar]
- Desmoulière A, Rubbia-Brandt L, Grau G, Gabbiani G. Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts. Lab Invest. 1992 Dec;67(6):716–726. [Abstract] [Google Scholar]
- Deuel TF, Kawahara RS, Mustoe TA, Pierce AF. Growth factors and wound healing: platelet-derived growth factor as a model cytokine. Annu Rev Med. 1991;42:567–584. [Abstract] [Google Scholar]
- Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986 Dec 25;315(26):1650–1659. [Abstract] [Google Scholar]
- Eddy RJ, Petro JA, Tomasek JJ. Evidence for the nonmuscle nature of the "myofibroblast" of granulation tissue and hypertropic scar. An immunofluorescence study. Am J Pathol. 1988 Feb;130(2):252–260. [Europe PMC free article] [Abstract] [Google Scholar]
- el-Torkey M, Giltman LI, Dabbous M. Collagens in scar carcinoma of the lung. Am J Pathol. 1985 Nov;121(2):322–326. [Europe PMC free article] [Abstract] [Google Scholar]
- Flanders KC, Roberts AB, Ling N, Fleurdelys BE, Sporn MB. Antibodies to peptide determinants in transforming growth factor beta and their applications. Biochemistry. 1988 Jan 26;27(2):739–746. [Abstract] [Google Scholar]
- Gabbiani G, Ryan GB, Majne G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971 May 15;27(5):549–550. [Abstract] [Google Scholar]
- Gabbiani G, Le Lous M, Bailey AJ, Bazin S, Delaunay A. Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunologic study. Virchows Arch B Cell Pathol. 1976 Aug 11;21(2):133–145. [Abstract] [Google Scholar]
- Gabbiani G, Gabbiani F, Heimark RL, Schwartz SM. Organization of actin cytoskeleton during early endothelial regeneration in vitro. J Cell Sci. 1984 Mar;66:39–50. [Abstract] [Google Scholar]
- Gospodarowicz D, Delgado D, Vlodavsky I. Permissive effect of the extracellular matrix on cell proliferation in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4094–4098. [Europe PMC free article] [Abstract] [Google Scholar]
- Grau GE, Fajardo LF, Piguet PF, Allet B, Lambert PH, Vassalli P. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science. 1987 Sep 4;237(4819):1210–1212. [Abstract] [Google Scholar]
- Ignotz RA, Massagué J. 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):4337–4345. [Abstract] [Google Scholar]
- Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzi P, Gordon K, Gown AM. 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):847–858. [Europe PMC free article] [Abstract] [Google Scholar]
- Kao RT, Hall J, Engel L, Stern R. The matrix of human breast tumor cells is mitogenic for fibroblasts. Am J Pathol. 1984 Apr;115(1):109–116. [Europe PMC free article] [Abstract] [Google Scholar]
- Kapanci Y, Burgan S, Pietra GG, Conne B, Gabbiani G. Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension. Am J Pathol. 1990 Apr;136(4):881–889. [Europe PMC free article] [Abstract] [Google Scholar]
- Kocher O, Skalli O, Bloom WS, Gabbiani G. Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening. Lab Invest. 1984 Jun;50(6):645–652. [Abstract] [Google Scholar]
- Kocher O, Skalli O, Cerutti D, Gabbiani F, Gabbiani G. Cytoskeletal features of rat aortic cells during development. An electron microscopic, immunohistochemical, and biochemical study. Circ Res. 1985 Jun;56(6):829–838. [Abstract] [Google Scholar]
- Kovacs EJ. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today. 1991 Jan;12(1):17–23. [Abstract] [Google Scholar]
- Krummel TM, Michna BA, Thomas BL, Sporn MB, Nelson JM, Salzberg AM, Cohen IK, Diegelmann RF. Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model. J Pediatr Surg. 1988 Jul;23(7):647–652. [Abstract] [Google Scholar]
- Kuhn C, McDonald JA. 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):1257–1265. [Europe PMC free article] [Abstract] [Google Scholar]
- Kumar RK, O'Grady R, Li W, Smith LW, Rhodes GC. Primary culture of adult mouse lung fibroblasts in serum-free medium: responses to growth factors. Exp Cell Res. 1991 Apr;193(2):398–404. [Abstract] [Google Scholar]
- Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [Abstract] [Google Scholar]
- Laiho M, Saksela O, Andreasen PA, Keski-Oja J. 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):2403–2410. [Europe PMC free article] [Abstract] [Google Scholar]
- Leof EB, Proper JA, Getz MJ, Moses HL. Transforming growth factor type beta regulation of actin mRNA. J Cell Physiol. 1986 Apr;127(1):83–88. [Abstract] [Google Scholar]
- Massagué J, Cheifetz S, Laiho M, Ralph DA, Weis FM, Zentella A. Transforming growth factor-beta. Cancer Surv. 1992;12:81–103. [Abstract] [Google Scholar]
- Matrisian LM, Leroy P, Ruhlmann C, Gesnel MC, Breathnach R. Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts. Mol Cell Biol. 1986 May;6(5):1679–1686. [Europe PMC free article] [Abstract] [Google Scholar]
- McCaffrey TA, Falcone DJ, Brayton CF, Agarwal LA, Welt FG, Weksler BB. 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):441–448. [Europe PMC free article] [Abstract] [Google Scholar]
- McCaffrey TA, Falcone DJ, Du B. 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):430–440. [Abstract] [Google Scholar]
- McHugh KM, Crawford K, Lessard JL. A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat. Dev Biol. 1991 Dec;148(2):442–458. [Abstract] [Google Scholar]
- Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. 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):7035–7056. [Europe PMC free article] [Abstract] [Google Scholar]
- Mitchell J, Woodcock-Mitchell J, Reynolds S, Low R, Leslie K, Adler K, Gabbiani G, Skalli O. Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung. Lab Invest. 1989 May;60(5):643–650. [Abstract] [Google Scholar]
- Pierce GF, Vande Berg J, Rudolph R, Tarpley J, Mustoe TA. 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):629–646. [Europe PMC free article] [Abstract] [Google Scholar]
- Pierce GF, Tarpley JE, Yanagihara D, Mustoe TA, Fox GM, Thomason A. 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):1375–1388. [Europe PMC free article] [Abstract] [Google Scholar]
- Piguet PF, Grau GE, Vassalli P. 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):103–110. [Europe PMC free article] [Abstract] [Google Scholar]
- Ramadori G. 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):147–158. [Abstract] [Google Scholar]
- Ramadori G, Rieder H, Knittel T, Dienes HP, Meyer zum Büschenfelde KH. Fat storing cells (FSC) of rat liver synthesize and secrete fibronectin. Comparison with hepatocytes. J Hepatol. 1987 Apr;4(2):190–197. [Abstract] [Google Scholar]
- Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al. 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):4167–4171. [Europe PMC free article] [Abstract] [Google Scholar]
- Robson MC. Growth factors as wound healing agents. Curr Opin Biotechnol. 1991 Dec;2(6):863–867. [Abstract] [Google Scholar]
- Rubbia-Brandt L, Sappino AP, Gabbiani G. 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. [Abstract] [Google Scholar]
- Rubenstein PA. The functional importance of multiple actin isoforms. Bioessays. 1990 Jul;12(7):309–315. [Abstract] [Google Scholar]
- Sappino AP, Masouyé I, Saurat JH, Gabbiani G. Smooth muscle differentiation in scleroderma fibroblastic cells. Am J Pathol. 1990 Sep;137(3):585–591. [Europe PMC free article] [Abstract] [Google Scholar]
- Sappino AP, Schürch W, Gabbiani G. Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest. 1990 Aug;63(2):144–161. [Abstract] [Google Scholar]
- Schäfer S, Zerbe O, Gressner AM. The synthesis of proteoglycans in fat-storing cells of rat liver. Hepatology. 1987 Jul-Aug;7(4):680–687. [Abstract] [Google Scholar]
- Schmitt-Gräff A, Krüger S, Bochard F, Gabbiani G, Denk H. 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):1233–1242. [Europe PMC free article] [Abstract] [Google Scholar]
- Schürch W, Seemayer TA, Lagacé R. 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):125–139. [Abstract] [Google Scholar]
- Shah M, Foreman DM, Ferguson MW. Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta. Lancet. 1992 Jan 25;339(8787):213–214. [Abstract] [Google Scholar]
- Shum DT, McFarlane RM. Histogenesis of Dupuytren's disease: an immunohistochemical study of 30 cases. J Hand Surg Am. 1988 Jan;13(1):61–67. [Abstract] [Google Scholar]
- Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986 Dec;103(6 Pt 2):2787–2796. [Europe PMC free article] [Abstract] [Google Scholar]
- Skalli O, Pelte MF, Peclet MC, Gabbiani G, Gugliotta P, Bussolati G, Ravazzola M, Orci L. 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):315–321. [Abstract] [Google Scholar]
- Skalli O, Schürch W, Seemayer T, Lagacé R, Montandon D, Pittet B, Gabbiani G. Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest. 1989 Feb;60(2):275–285. [Abstract] [Google Scholar]
- Sporn MB, Roberts AB. Interactions of retinoids and transforming growth factor-beta in regulation of cell differentiation and proliferation. Mol Endocrinol. 1991 Jan;5(1):3–7. [Abstract] [Google Scholar]
- Sporn MB, Roberts AB. Transforming growth factor-beta: recent progress and new challenges. J Cell Biol. 1992 Dec;119(5):1017–1021. [Europe PMC free article] [Abstract] [Google Scholar]
- Sporn MB, Roberts AB, Wakefield LM, de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol. 1987 Sep;105(3):1039–1045. [Europe PMC free article] [Abstract] [Google Scholar]
- Thornton SC, Por SB, Walsh BJ, Penny R, Breit SN. Interaction of immune and connective tissue cells: I. The effect of lymphokines and monokines on fibroblast growth. J Leukoc Biol. 1990 Apr;47(4):312–320. [Abstract] [Google Scholar]
- Towbin H, Staehelin T, Gordon J. 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):4350–4354. [Europe PMC free article] [Abstract] [Google Scholar]
- Vogel A, Raines E, Kariya B, Rivest MJ, Ross R. 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):2810–2814. [Europe PMC free article] [Abstract] [Google Scholar]
Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press
Full text links
Read article at publisher's site: https://doi.org/10.1083/jcb.122.1.103
Read article for free, from open access legal sources, via Unpaywall: https://rupress.org/jcb/article-pdf/122/1/103/1258198/103.pdf
Citations & impact
Impact metrics
Citations of article over time
Alternative metrics
Smart citations by scite.ai
Explore citation contexts and check if this article has been
supported or disputed.
https://scite.ai/reports/10.1083/jcb.122.1.103
Article citations
Evidence of the Link between Stroma Remodeling and Prostate Cancer Prognosis.
Cancers (Basel), 16(18):3215, 21 Sep 2024
Cited by: 0 articles | PMID: 39335188 | PMCID: PMC11430343
Review Free full text in Europe PMC
Effect of Electromagnetic Field on Proliferation and Migration of Fibroblasts and Keratinocytes: Implications in Wound Healing and Regeneration.
J Biotechnol Biomed, 7(3):387-399, 04 Sep 2024
Cited by: 0 articles | PMID: 39364330 | PMCID: PMC11448841
ALKBH5-mediated m6A demethylation ameliorates extracellular matrix deposition in cutaneous pathological fibrosis.
Clin Transl Med, 14(9):e70016, 01 Sep 2024
Cited by: 1 article | PMID: 39233335 | PMCID: PMC11374695
Recombinant collagen for the repair of skin wounds and photo-aging damage.
Regen Biomater, 11:rbae108, 02 Sep 2024
Cited by: 0 articles | PMID: 39323745 | PMCID: PMC11422187
Mini review on collagens in normal skin and pathological scars: current understanding and future perspective.
Front Med (Lausanne), 11:1449597, 18 Jul 2024
Cited by: 1 article | PMID: 39091289 | PMCID: PMC11291465
Review Free full text in Europe PMC
Go to all (1,371) article citations
Similar Articles
To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.
Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity.
Virchows Arch, 425(1):3-24, 01 Jan 1994
Cited by: 224 articles | PMID: 7921410
Review
Locally applied GM-CSF induces the accumulation of alpha-smooth muscle actin containing myofibroblasts.
Virchows Arch B Cell Pathol Incl Mol Pathol, 60(2):73-82, 01 Jan 1991
Cited by: 49 articles | PMID: 1675512
Induction of alpha-smooth muscle actin expression and myofibroblast transformation in cultured corneal keratocytes.
Cornea, 15(5):505-516, 01 Sep 1996
Cited by: 188 articles | PMID: 8862928
Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts.
Lab Invest, 67(6):716-726, 01 Dec 1992
Cited by: 66 articles | PMID: 1460862