This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vyalov, S. L. Articles by Kapanci, Y. Search for Related Content PubMed PubMed Citation Articles by Vyalov, S. L. Articles by Kapanci, Y.

American Journal of Pathology, Vol 143, 1754-1765, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Rat alveolar myofibroblasts acquire alpha-smooth muscle actin expression during bleomycin-induced pulmonary fibrosis

SL Vyalov, G Gabbiani and Y Kapanci
Department of Pathology, Centre Medical Universitaire, Geneva, Switzerland.

The majority of fibroblasts in alveolar septa are characterized by the presence of cytoplasmic bundles of microfilaments that contain cytoplasmic actin isoforms; these cells have been named contractile interstitial cells or V-type myofibroblasts. In the rat, they express desmin as intermediate filament protein. In this study, we explored the possibility that modulation and replication of such septal fibroblasts result in the appearance of alpha-smooth muscle (alpha-SM) actin- positive myofibroblasts, typical of lung fibrosis. Experimental pulmonary fibrosis was produced by a unique intratracheal instillation of bleomycin to 28 rats. Eight additional rats used as controls received the equivalent volume of saline. Paraffin and frozen sections of lungs were examined at days 1, 3, 5 and 7 after treatment. Microfilaments and intermediate filaments were stained using antibodies against total actin, alpha-SM actin, desmin, vimentin, keratin, and SM myosin. Electron microscopic labeling of desmin and alpha-SM actin using immunogold technique was done on Lowicryl K4M resin-embedded specimens. alpha-SM actin appeared in desmin-positive alveolar fibroblasts as early as 24 hours after intratracheal bleomycin instillation; the modulation of alpha-SM actin in these cells was preceded by a lymphomonocytic infiltration of alveolar septa. Twenty- four hours to 3 days after bleomycin administration, a proliferation of alveolar myofibroblasts occurred. Fibrosis with laying down of collagen fibers took place after the above mentioned cellular modifications. Our results support the view that septal fibroblastic cells can modulate into typical alpha-SM actin-containing myofibroblasts during experimental bleomycin-induced pulmonary fibrosis. In such a modulation a possible role of cytokines, particularly of transforming growth factor-beta, is considered.

This article has been cited by other articles:

				E. Tourkina, M. Richard, P. Gooz, M. Bonner, J. Pannu, R. Harley, P. N. Bernatchez, W. C. Sessa, R. M. Silver, and S. Hoffman Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L843 - L861. [Abstract] [Full Text] [PDF]

				T. Liu, R. R. Warburton, O. E. Guevara, N. S. Hill, B. L. Fanburg, M. Gaestel, and U. S. Kayyali Lack of MK2 Inhibits Myofibroblast Formation and Exacerbates Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 507 - 517. [Abstract] [Full Text] [PDF]

				A. Pagano, I. Metrailler-Ruchonnet, M. Aurrand-Lions, M. Lucattelli, Y. Donati, and C. B. Argiroffo Poly(ADP-ribose) polymerase-1 (PARP-1) controls lung cell proliferation and repair after hyperoxia-induced lung damage Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L619 - L629. [Abstract] [Full Text] [PDF]

				W. E. Lawson, V. V. Polosukhin, O. Zoia, G. T. Stathopoulos, W. Han, D. Plieth, J. E. Loyd, E. G. Neilson, and T. S. Blackwell Characterization of Fibroblast-specific Protein 1 in Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 899 - 907. [Abstract] [Full Text] [PDF]

				T. Kakugawa, H. Mukae, T. Hayashi, H. Ishii, K. Abe, T. Fujii, H. Oku, M. Miyazaki, J. Kadota, and S. Kohno Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis Eur. Respir. J., July 1, 2004; 24(1): 57 - 65. [Abstract] [Full Text] [PDF]

				M. Short, R. A. Nemenoff, W. M. Zawada, K. R. Stenmark, and M. Das Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblasts Am J Physiol Cell Physiol, February 1, 2004; 286(2): C416 - C425. [Abstract] [Full Text]

				J. E. Kolodsick, M. Peters-Golden, J. Larios, G. B. Toews, V. J. Thannickal, and B. B. Moore Prostaglandin E2 Inhibits Fibroblast to Myofibroblast Transition via E. Prostanoid Receptor 2 Signaling and Cyclic Adenosine Monophosphate Elevation Am. J. Respir. Cell Mol. Biol., November 1, 2003; 29(5): 537 - 544. [Abstract] [Full Text]

				G. S. Bogatkevich, E. Tourkina, C. S. Abrams, R. A. Harley, R. M. Silver, and A. Ludwicka-Bradley Contractile activity and smooth muscle {alpha}-actin organization in thrombin-induced human lung myofibroblasts Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L334 - L343. [Abstract] [Full Text] [PDF]

				J. Condon, S. Yin, B. Mayhew, R. A. Word, W.E. Wright, J.W. Shay, and W. E. Rainey Telomerase Immortalization of Human Myometrial Cells Biol Reprod, August 1, 2002; 67(2): 506 - 514. [Abstract] [Full Text] [PDF]

				R. Koslowski, U. Pfeil, H. Fehrenbach, M. Kasper, E. Skutelsky, and K-W. Wenzel Changes in xylosyltransferase activity and in proteoglycan deposition in bleomycin-induced lung injury in rat Eur. Respir. J., August 1, 2001; 18(2): 347 - 356. [Abstract] [Full Text] [PDF]

				S. HASHIMOTO, Y. GON, I. TAKESHITA, K. MATSUMOTO, S. MARUOKA, and T. HORIE Transforming Growth Factor-{beta}1 Induces Phenotypic Modulation of Human Lung Fibroblasts to Myofibroblast Through a c-Jun-NH2-Terminal Kinase-Dependent Pathway Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 152 - 157. [Abstract] [Full Text]

				D. Levine, D. C. Rockey, T. A. Milner, J. M. Breuss, J. T. Fallon, and L. M. Schnapp Expression of the Integrin {alpha}8{beta}1 during Pulmonary and Hepatic Fibrosis Am. J. Pathol., June 1, 2000; 156(6): 1927 - 1935. [Abstract] [Full Text] [PDF]

				M. DOLHNIKOFF, T. MAUAD, and M. S. LUDWIG Extracellular Matrix and Oscillatory Mechanics of Rat Lung Parenchyma in Bleomycin-induced Fibrosis Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1750 - 1757. [Abstract] [Full Text]

				R. Jones, M. Jacobson, and W. Steudel alpha -Smooth-Muscle Actin and Microvascular Precursor Smooth-Muscle Cells in Pulmonary Hypertension Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 582 - 594. [Abstract] [Full Text]

				T. Z. Kirk, M. E. Mark, C. C. Chua, B. H. Chua, and M. D. Mayes Myofibroblasts from Scleroderma Skin Synthesize Elevated Levels of Collagen and Tissue Inhibitor of Metalloproteinase (TIMP-1) with Two Forms of TIMP-1 J. Biol. Chem., February 17, 1995; 270(7): 3423 - 3428. [Abstract] [Full Text] [PDF]

				G. S. Bogatkevich, E. Tourkina, R. M. Silver, and A. Ludwicka-Bradley Thrombin Differentiates Normal Lung Fibroblasts to a Myofibroblast Phenotype via the Proteolytically Activated Receptor-1 and a Protein Kinase C-dependent Pathway J. Biol. Chem., November 21, 2001; 276(48): 45184 - 45192. [Abstract] [Full Text] [PDF]

				R. P. Bowler, M. Nicks, K. Warnick, and J. D. Crapo Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L719 - L726. [Abstract] [Full Text] [PDF]