Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Sep;137(3):585–591.

Smooth muscle differentiation in scleroderma fibroblastic cells.

A P Sappino 1, I Masouyé 1, J H Saurat 1, G Gabbiani 1
PMCID: PMC1877526  PMID: 1698026

Abstract

Using antibodies to alpha-smooth muscle actin and desmin on paraffin-embedded formalin-fixed tissue sections, the authors demonstrate that fibroblastic cells of localized and systemic scleroderma lesions express features of smooth muscle differentiation. Eleven of eleven skin specimens of systemic sclerosis patients and two of four skin specimens of localized scleroderma displayed the presence of fibroblasts expressing alpha-smooth muscle actin, a cell population that predominated in areas of prominent collagen deposition. A similar fibroblastic phenotype was found in the esophagus, the liver, and the lung specimens obtained from four patients who died of progressive systemic sclerosis. Immunostaining for desmin, performed on adjacent tissue sections, demonstrated that a minority of these fibroblastic cells present in skin and visceral lesions contained this protein. The authors' observations indicate that scleroderma fibroblasts are phenotypically related to the stromal cells previously identified in hypertrophic scars, fibromatoses, and desmoplasia; they might provide novel criteria for the characterization of scleroderma lesions and help to identify the factors responsible for phenotypic modulations in fibroblastic cells.

Full text

PDF
585

Images in this article

587Figure 1
on p.587
587Figure 2
on p.587
588Figure 3
on p.588

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnett A. J., Miller M. H., Littlejohn G. O. A survival study of patients with scleroderma diagnosed over 30 years (1953-1983): the value of a simple cutaneous classification in the early stages of the disease. J Rheumatol. 1988 Feb;15(2):276–283. [PubMed] [Google Scholar]
  2. Buckingham R. B., Prince R. K., Rodnan G. P. Progressive systemic sclerosis (PSS, scleroderma) dermal fibroblasts synthesize increased amounts of glycosaminoglycan. J Lab Clin Med. 1983 May;101(5):659–669. [PubMed] [Google Scholar]
  3. Buckingham R. B., Prince R. K., Rodnan G. P., Taylor F. Increased collagen accumulation in dermal fibroblast cultures from patients with progressive systemic sclerosis (scleroderma). J Lab Clin Med. 1978 Jul;92(1):5–21. [PubMed] [Google Scholar]
  4. D'Angelo W. A., Fries J. F., Masi A. T., Shulman L. E. Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med. 1969 Mar;46(3):428–440. doi: 10.1016/0002-9343(69)90044-8. [DOI] [PubMed] [Google Scholar]
  5. Duncan M. R., Berman B. Persistence of a reduced-collagen-producing phenotype in cultured scleroderma fibroblasts after short-term exposure to interferons. J Clin Invest. 1987 May;79(5):1318–1324. doi: 10.1172/JCI112956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Falanga V., Tiegs S. L., Alstadt S. P., Roberts A. B., Sporn M. B. Transforming growth factor-beta: selective increase in glycosaminoglycan synthesis by cultures of fibroblasts from patients with progressive systemic sclerosis. J Invest Dermatol. 1987 Jul;89(1):100–104. doi: 10.1111/1523-1747.ep12580445. [DOI] [PubMed] [Google Scholar]
  7. Fleischmajer R., Perlish J. S., Duncan M. Scleroderma. A model for fibrosis. Arch Dermatol. 1983 Dec;119(12):957–962. doi: 10.1001/archderm.119.12.957. [DOI] [PubMed] [Google Scholar]
  8. Fleischmajer R., Perlish J. S. Glycosaminoglycans in scleroderma and scleredema. J Invest Dermatol. 1972 Mar;58(3):129–132. doi: 10.1111/1523-1747.ep12538919. [DOI] [PubMed] [Google Scholar]
  9. Fleischmajer R., Perlish J. S., Krieg T., Timpl R. Variability in collagen and fibronectin synthesis by scleroderma fibroblasts in primary culture. J Invest Dermatol. 1981 May;76(5):400–403. doi: 10.1111/1523-1747.ep12520933. [DOI] [PubMed] [Google Scholar]
  10. Fleischmajer R., Perlish J. S., West W. P. Ultrastructure of cutaneous cellular infiltrates in scleroderma. Arch Dermatol. 1977 Dec;113(12):1661–1666. [PubMed] [Google Scholar]
  11. Gabbiani G., Ryan G. B., Majne G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971 May 15;27(5):549–550. doi: 10.1007/BF02147594. [DOI] [PubMed] [Google Scholar]
  12. Hansson G. K., Hellstrand M., Rymo L., Rubbia L., Gabbiani G. Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells. J Exp Med. 1989 Nov 1;170(5):1595–1608. doi: 10.1084/jem.170.5.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Horwitz D. A., Garrett M. A. Lymphocyte reactivity to mitogens in subjects with systemic lupus erythematosus, rheumatoid arthritis and scleroderma. Clin Exp Immunol. 1977 Jan;27(1):92–99. [PMC free article] [PubMed] [Google Scholar]
  14. Inoshita T., Whiteside T. L., Rodnan G. P., Taylor F. H. Abnormalities of T lymphocyte subsets in patients with progressive systemic sclerosis (PSS, scleroderma). J Lab Clin Med. 1981 Feb;97(2):264–277. [PubMed] [Google Scholar]
  15. Leroy E. C. Connective tissue synthesis by scleroderma skin fibroblasts in cell culture. J Exp Med. 1972 Jun 1;135(6):1351–1362. doi: 10.1084/jem.135.6.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miettinen M. Immunostaining of intermediate filament proteins in paraffin sections. Evaluation of optimal protease treatment to improve the immunoreactivity. Pathol Res Pract. 1989 Apr;184(4):431–436. doi: 10.1016/S0344-0338(89)80039-1. [DOI] [PubMed] [Google Scholar]
  17. Morse J. H., Bodi B. S. Autologous and allogeneic mixed lymphocyte reactions in progressive systemic sclerosis. Arthritis Rheum. 1982 Apr;25(4):390–395. doi: 10.1002/art.1780250405. [DOI] [PubMed] [Google Scholar]
  18. Peres R., Betsholtz C., Westermark B., Heldin C. H. Frequent expression of growth factors for mesenchymal cells in human mammary carcinoma cell lines. Cancer Res. 1987 Jul 1;47(13):3425–3429. [PubMed] [Google Scholar]
  19. Perlish J. S., Bashey R. I., Stephens R. E., Fleischmajer R. Connective tissue synthesis by cultured scleroderma fibroblasts. I. In vitro collagen synthesis by normal and scleroderma dermal fibroblasts. Arthritis Rheum. 1976 Sep-Oct;19(5):891–901. doi: 10.1002/art.1780190510. [DOI] [PubMed] [Google Scholar]
  20. Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosenbloom J., Feldman G., Freundlich B., Jimenez S. A. Inhibition of excessive scleroderma fibroblast collagen production by recombinant gamma-interferon. Association with a coordinate decrease in types I and III procollagen messenger RNA levels. Arthritis Rheum. 1986 Jul;29(7):851–856. doi: 10.1002/art.1780290706. [DOI] [PubMed] [Google Scholar]
  22. Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
  23. Roumm A. D., Whiteside T. L., Medsger T. A., Jr, Rodnan G. P. Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984 Jun;27(6):645–653. doi: 10.1002/art.1780270607. [DOI] [PubMed] [Google Scholar]
  24. Rungger-Brändle E., Gabbiani G. The role of cytoskeletal and cytocontractile elements in pathologic processes. Am J Pathol. 1983 Mar;110(3):361–392. [PMC free article] [PubMed] [Google Scholar]
  25. Sappino A. P., Skalli O., Jackson B., Schürch W., Gabbiani G. Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues. Int J Cancer. 1988 May 15;41(5):707–712. doi: 10.1002/ijc.2910410512. [DOI] [PubMed] [Google Scholar]
  26. Seemayer T. A., Schürch W., Lagacé R. Myofibroblasts in human pathology. Hum Pathol. 1981 Jun;12(6):491–492. doi: 10.1016/s0046-8177(81)80061-5. [DOI] [PubMed] [Google Scholar]
  27. 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. doi: 10.1083/jcb.103.6.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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. [PubMed] [Google Scholar]
  29. Sporn M. B., Roberts A. B. Peptide growth factors and inflammation, tissue repair, and cancer. J Clin Invest. 1986 Aug;78(2):329–332. doi: 10.1172/JCI112580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sporn M. B., Roberts A. B., Wakefield L. M., 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. doi: 10.1083/jcb.105.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tajima S., Pinnell S. R. Collagen synthesis by human skin fibroblasts in culture: studies of fibroblasts explanted from papillary and reticular dermis. J Invest Dermatol. 1981 Nov;77(5):410–412. doi: 10.1111/1523-1747.ep12494614. [DOI] [PubMed] [Google Scholar]
  32. Toccanier-Pelte M. F., Skalli O., Kapanci Y., Gabbiani G. Characterization of stromal cells with myoid features in lymph nodes and spleen in normal and pathologic conditions. Am J Pathol. 1987 Oct;129(1):109–118. [PMC free article] [PubMed] [Google Scholar]
  33. Whiteside T. L., Worrall J. G., Prince R. K., Buckingham R. B., Rodnan G. P. Soluble mediators from mononuclear cells increase the synthesis of glycosaminoglycan by dermal fibroblast cultures derived from normal subjects and progressive systemic sclerosis patients. Arthritis Rheum. 1985 Feb;28(2):188–197. doi: 10.1002/art.1780280214. [DOI] [PubMed] [Google Scholar]
  34. Yokoi Y., Namihisa T., Kuroda H., Komatsu I., Miyazaki A., Watanabe S., Usui K. Immunocytochemical detection of desmin in fat-storing cells (Ito cells). Hepatology. 1984 Jul-Aug;4(4):709–714. doi: 10.1002/hep.1840040425. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES