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 Coker, R. K. Articles by McAnulty, R. J. Search for Related Content PubMed PubMed Citation Articles by Coker, R. K. Articles by McAnulty, R. J.

American Journal of Pathology, Vol 150, 981-991, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis

RK Coker, GJ Laurent, S Shahzeidi, PA Lympany, RM du Bois, PK Jeffery and RJ McAnulty
Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, University College London Medical School, United Kingdom.

Transforming growth factor (TGF)-beta 1 may potentiate wound healing and fibrosis by stimulating fibroblast collagen deposition. TGF-beta 1 is implicated in the pathogenesis of pulmonary fibrosis, but the role of TGF-beta 2 and TGF-beta 3 remains unclear. We examined their effects on lung fibroblast procollagen metabolism in vitro and localized their gene expression during bleomycin-induced lung fibrosis using in situ hybridization with digoxigenin-labeled riboprobes. All three isoforms stimulated fibroblast procollagen production. TGF-beta 3 was the most potent and also reduced procollagen degradation. In normal mouse lung, TGF-beta 1 and TGF-beta 3 mRNA transcripts were abundant in bronchiolar epithelium. After bleomycin, TGF-beta 1 gene expression was maximally enhanced at 10 days, with the signal being predominant in macrophages. Signal was also enhanced in mesenchymal, pulmonary endothelial, and mesothelial cells. After 35 days, the pattern of TGF-beta 1 gene expression returned to that of control lung. TGF-beta 3 gene expression remained unchanged throughout compared with controls. TGF-beta 2 mRNA was not detected with the antisense probe, but signal obtained with the sense probe suggests the presence of a naturally occurring antisense. This study demonstrates that TGF-beta 1, -beta 2, and -beta 3 all exert profibrotic effects in vitro. However, TGF-beta isoform gene expression is differentially controlled during experimental pulmonary fibrosis with TGF-beta 1 the predominant isoform expressed during pathogenesis.

This article has been cited by other articles:

				G. J. Laurent, R. J. McAnulty, M. Hill, and R. Chambers Escape from the Matrix: Multiple Mechanisms for Fibroblast Activation in Pulmonary Fibrosis Proceedings of the ATS, April 15, 2008; 5(3): 311 - 315. [Abstract] [Full Text] [PDF]

				T J Williams and J W Wilson Challenges in pulmonary fibrosis: 7 {middle dot} Novel therapies and lung transplantation Thorax, March 1, 2008; 63(3): 277 - 284. [Abstract] [Full Text] [PDF]

				N. I. Chaudhary, G. J. Roth, F. Hilberg, J. Muller-Quernheim, A. Prasse, G. Zissel, A. Schnapp, and J. E. Park Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis Eur. Respir. J., May 1, 2007; 29(5): 976 - 985. [Abstract] [Full Text] [PDF]

				Y. Ishida, A. Kimura, T. Kondo, T. Hayashi, M. Ueno, N. Takakura, K. Matsushima, and N. Mukaida Essential Roles of the CC Chemokine Ligand 3-CC Chemokine Receptor 5 Axis in Bleomycin-Induced Pulmonary Fibrosis through Regulation of Macrophage and Fibrocyte Infiltration Am. J. Pathol., March 1, 2007; 170(3): 843 - 854. [Abstract] [Full Text] [PDF]

				P. Li, S. Oparil, L. Novak, X. Cao, W. Shi, J. Lucas, and Y.-F. Chen ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells J Appl Physiol, January 1, 2007; 102(1): 390 - 398. [Abstract] [Full Text] [PDF]

				F. Chua, S. E. Dunsmore, P. H. Clingen, S. E. Mutsaers, S. D. Shapiro, A. W. Segal, J. Roes, and G. J. Laurent Mice Lacking Neutrophil Elastase Are Resistant to Bleomycin-Induced Pulmonary Fibrosis Am. J. Pathol., January 1, 2007; 170(1): 65 - 74. [Abstract] [Full Text] [PDF]

				M. Horikawa, M. Fujimoto, M. Hasegawa, T. Matsushita, Y. Hamaguchi, A. Kawasuji, Y. Matsushita, T. Fujita, F. Ogawa, K. Takehara, et al. E- and P-Selectins Synergistically Inhibit Bleomycin-Induced Pulmonary Fibrosis Am. J. Pathol., September 1, 2006; 169(3): 740 - 749. [Abstract] [Full Text] [PDF]

				A. M. Kapoun, N. J. Gaspar, Y. Wang, D. Damm, Y.-W. Liu, G. O'Young, D. Quon, A. Lam, K. Munson, T.-T. Tran, et al. Transforming Growth Factor-beta Receptor Type 1 (TGFbetaRI) Kinase Activity but Not p38 Activation Is Required for TGFbetaRI-Induced Myofibroblast Differentiation and Profibrotic Gene Expression Mol. Pharmacol., August 1, 2006; 70(2): 518 - 531. [Abstract] [Full Text] [PDF]

				A. Kruit, J. C. Grutters, H. J. T. Ruven, C. H. M. van Moorsel, R. Weiskirchen, S. Mengsteab, and J. M. M. van den Bosch Transforming Growth Factor-{beta} Gene Polymorphisms in Sarcoidosis Patients With and Without Fibrosis Chest, June 1, 2006; 129(6): 1584 - 1591. [Abstract] [Full Text] [PDF]

				C. Karagiannidis, V. Velehorschi, B. Obertrifter, H.-N. Macha, A. Linder, and L. Freitag High-Level Expression of Matrix-Associated Transforming Growth Factor-{beta}1 in Benign Airway Stenosis Chest, May 1, 2006; 129(5): 1298 - 1304. [Abstract] [Full Text] [PDF]

				N. I. Chaudhary, A. Schnapp, and J. E. Park Pharmacologic Differentiation of Inflammation and Fibrosis in the Rat Bleomycin Model Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 769 - 776. [Abstract] [Full Text] [PDF]

				Y.-F. Chen, J.-A. Feng, P. Li, D. Xing, Y. Zhang, R. Serra, N. Ambalavanan, E. Majid-Hassan, and S. Oparil Dominant negative mutation of the TGF-beta receptor blocks hypoxia-induced pulmonary vascular remodeling J Appl Physiol, February 1, 2006; 100(2): 564 - 571. [Abstract] [Full Text] [PDF]

				W. Matsuyama, M. Watanabe, Y. Shirahama, R. Hirano, H. Mitsuyama, I. Higashimoto, M. Osame, and K. Arimura Suppression of Discoidin Domain Receptor 1 by RNA Interference Attenuates Lung Inflammation J. Immunol., February 1, 2006; 176(3): 1928 - 1936. [Abstract] [Full Text] [PDF]

				B. B. Moore, J. E. Kolodsick, V. J. Thannickal, K. Cooke, T. A. Moore, C. Hogaboam, C. A. Wilke, and G. B. Toews CCR2-Mediated Recruitment of Fibrocytes to the Alveolar Space after Fibrotic Injury Am. J. Pathol., March 1, 2005; 166(3): 675 - 684. [Abstract] [Full Text] [PDF]

				J. Yamate, Y. Machida, M. Ide, M. Kuwamura, T. Kotani, O. Sawamoto, and J. LaMarre Cisplatin-Induced Renal Interstitial Fibrosis in Neonatal Rats, Developing as Solitary Nephron Unit Lesions Toxicol Pathol, February 1, 2005; 33(2): 207 - 217. [Abstract] [Full Text] [PDF]

				R. Aghanouri, M. Ghanei, J. Aslani, H. Keivani-Amine, F. Rastegar, and A. Karkhane Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1160 - L1164. [Abstract] [Full Text] [PDF]

				A. LEASK and D. J. ABRAHAM TGF-{beta} signaling and the fibrotic response FASEB J, May 1, 2004; 18(7): 816 - 827. [Abstract] [Full Text] [PDF]

				I. Inoshima, K. Kuwano, N. Hamada, N. Hagimoto, M. Yoshimi, T. Maeyama, A. Takeshita, S. Kitamoto, K. Egashira, and N. Hara Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice Am J Physiol Lung Cell Mol Physiol, May 1, 2004; 286(5): L1038 - L1044. [Abstract] [Full Text] [PDF]

				A. I. Jobling, M. Nguyen, A. Gentle, and N. A. McBrien Isoform-specific Changes in Scleral Transforming Growth Factor-{beta} Expression and the Regulation of Collagen Synthesis during Myopia Progression J. Biol. Chem., April 30, 2004; 279(18): 18121 - 18126. [Abstract] [Full Text] [PDF]

				U. Bartram and C. P. Speer The Role of Transforming Growth Factor {beta} in Lung Development and Disease Chest, February 1, 2004; 125(2): 754 - 765. [Abstract] [Full Text] [PDF]

				A. Gunther, N. Lubke, M. Ermert, R. T. Schermuly, N. Weissmann, A. Breithecker, P. Markart, C. Ruppert, K. Quanz, L. Ermert, et al. Prevention of Bleomycin-induced Lung Fibrosis by Aerosolization of Heparin or Urokinase in Rabbits Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1358 - 1365. [Abstract] [Full Text] [PDF]

				A. Kitani, I. Fuss, K. Nakamura, F. Kumaki, T. Usui, and W. Strober Transforming Growth Factor (TGF)-{beta}1-producing Regulatory T Cells Induce Smad-mediated Interleukin 10 Secretion That Facilitates Coordinated Immunoregulatory Activity and Amelioration of TGF-{beta}1-mediated Fibrosis J. Exp. Med., October 20, 2003; 198(8): 1179 - 1188. [Abstract] [Full Text] [PDF]

				W A Dik, R J McAnulty, M A Versnel, B A E Naber, L J I Zimmermann, G J Laurent, and S E Mutsaers Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats Thorax, September 1, 2003; 58(9): 765 - 771. [Abstract] [Full Text] [PDF]

				C. Jakubzick, E. S. Choi, S. L. Kunkel, B. H. Joshi, R. K. Puri, and C. M. Hogaboam Impact of Interleukin-13 Responsiveness on the Synthetic and Proliferative Properties of Th1- and Th2-Type Pulmonary Granuloma Fibroblasts Am. J. Pathol., May 1, 2003; 162(5): 1475 - 1486. [Abstract] [Full Text] [PDF]

				Y. Hamaguchi, Y. Nishizawa, M. Yasui, M. Hasegawa, Y. Kaburagi, K. Komura, T. Nagaoka, E. Saito, Y. Shimada, K. Takehara, et al. Intercellular Adhesion Molecule-1 and L-Selectin Regulate Bleomycin-Induced Lung Fibrosis Am. J. Pathol., November 1, 2002; 161(5): 1607 - 1618. [Abstract] [Full Text] [PDF]

				M. K. Winkler and J. L. Fowlkes Metalloproteinase and growth factor interactions: do they play a role in pulmonary fibrosis? Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L1 - L11. [Abstract] [Full Text] [PDF]

				E. Papakonstantinou, M. Roth, M. Tamm, O. Eickelberg, A. P. Perruchoud, and G. Karakiulakis Hypoxia Differentially Enhances the Effects of Transforming Growth Factor-beta Isoforms on the Synthesis and Secretion of Glycosaminoglycans by Human Lung Fibroblasts J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 830 - 837. [Abstract] [Full Text] [PDF]

				J. Yamate, K. Sato, M. Ide, M. Nakanishi, M. Kuwamura, S. Sakuma, and S. Nakatsuji Participation of Different Macrophage Populations and Myofibroblastic Cells in Chronically Developed Renal Interstitial Fibrosis after Cisplatin-induced Renal Injury in Rats Vet. Pathol., May 1, 2002; 39(3): 322 - 333. [Abstract] [Full Text] [PDF]

				J. M. Mason, H.-P. Xu, S. K. Rao, A. Leask, M. Barcia, J. Shan, R. Stephenson, and S. Tabibzadeh Lefty Contributes to the Remodeling of Extracellular Matrix by Inhibition of Connective Tissue Growth Factor and Collagen mRNA Expression and Increased Proteolytic Activity in a Fibrosarcoma Model J. Biol. Chem., January 4, 2002; 277(1): 407 - 415. [Abstract] [Full Text]

				W. J. Howat, S. T. Holgate, and P. M. Lackie TGF-beta isoform release and activation during in vitro bronchial epithelial wound repair Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L115 - L123. [Abstract] [Full Text] [PDF]

				F. Lang and P. Cohen Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms Sci. Signal., November 13, 2001; 2001(108): re17 - re17. [Abstract] [Full Text] [PDF]

				B. B. Moore, R. Paine III, P. J. Christensen, T. A. Moore, S. Sitterding, R. Ngan, C. A. Wilke, W. A. Kuziel, and G. B. Toews Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling J. Immunol., October 15, 2001; 167(8): 4368 - 4377. [Abstract] [Full Text] [PDF]

				R K Coker, G J Laurent, P K Jeffery, R M du Bois, C M Black, and R J McAnulty Localisation of transforming growth factor {beta}1 and {beta}3 mRNA transcripts in normal and fibrotic human lung Thorax, July 1, 2001; 56(7): 549 - 556. [Abstract] [Full Text] [PDF]

				S. E. Dunsmore, J. Roes, F. J. Chua, A. W. Segal, S. E. Mutsaers, and G. J. Laurent Evidence That Neutrophil Elastase-Deficient Mice Are Resistant to Bleomycin-Induced Fibrosis Chest, July 1, 2001; 120(2007): 35S - 36S. [Full Text] [PDF]

				C. B. Keerthisingam, R. G. Jenkins, N. K. Harrison, N. A. Hernandez-Rodriguez, H. Booth, G. J. Laurent, S. L. Hart, M. L. Foster, and R. J. McAnulty Cyclooxygenase-2 Deficiency Results in a Loss of the Anti-Proliferative Response to Transforming Growth Factor-{beta} in Human Fibrotic Lung Fibroblasts and Promotes Bleomycin-Induced Pulmonary Fibrosis in Mice Am. J. Pathol., April 1, 2001; 158(4): 1411 - 1422. [Abstract] [Full Text] [PDF]

				O. EICKELBERG, A. PANSKY, E. KOEHLER, M. BIHL, M. TAMM, P. HILDEBRAND, A. P. PERRUCHOUD, M. KASHGARIAN, and M. ROTH Molecular mechanisms of TGF-{beta} antagonism by interferon {gamma} and cyclosporine A in lung fibroblasts FASEB J, March 1, 2001; 15(3): 797 - 806. [Abstract] [Full Text] [PDF]

				R. W. LIGHT, D.-S. CHENG, Y. C. G.  LEE, J. ROGERS, J. DAVIDSON, and K. B. LANE A Single Intrapleural Injection of Transforming Growth Factor-beta 2 Produces an Excellent Pleurodesis in Rabbits Am. J. Respir. Crit. Care Med., July 1, 2000; 162(1): 98 - 104. [Abstract] [Full Text]

				R. P. MARSHALL, R. J. MCANULTY, and G. J. LAURENT Angiotensin II Is Mitogenic for Human Lung Fibroblasts via Activation of the Type 1 Receptor Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1999 - 2004. [Abstract] [Full Text]

				P. PAAKKO, R. KAARTEENAHO-WIIK, R. POLLANEN, and Y. SOINI Tenascin mRNA Expression at the Foci of Recent Injury in Usual Interstitial Pneumonia Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 967 - 972. [Abstract] [Full Text] [PDF]

				A. Churg, B. Gilks, and J. Dai Induction of fibrogenic mediators by fine and ultrafine titanium dioxide in rat tracheal explants Am J Physiol Lung Cell Mol Physiol, November 1, 1999; 277(5): L975 - L982. [Abstract] [Full Text] [PDF]

				Q. Wang, Y. Wang, D. M Hyde, P. J Gotwals, V. E Koteliansky, S. T Ryan, and S. N Giri Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor in hamsters Thorax, September 1, 1999; 54(9): 805 - 812. [Abstract] [Full Text]

				F. Levi-Schaffer, E. Garbuzenko, A. Rubin, R. Reich, D. Pickholz, P. Gillery, H. Emonard, A. Nagler, and F. A. X. Maquart Human eosinophils regulate human lung- and skin-derived fibroblast properties in vitro: A role for transforming growth factor beta (TGF-beta ) PNAS, August 17, 1999; 96(17): 9660 - 9665. [Abstract] [Full Text] [PDF]

				O. Eickelberg, E. Kohler, F. Reichenberger, S. Bertschin, T. Woodtli, P. Erne, A. P. Perruchoud, and M. Roth Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-beta 1 and TGF-beta 3 Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L814 - L824. [Abstract] [Full Text] [PDF]

				J. DAI, B. GILKS, K. PRICE, and A. CHURG Mineral Dusts Directly Induce Epithelial and Interstitial Fibrogenic Mediators and Matrix Components in the Airway Wall Am. J. Respir. Crit. Care Med., December 1, 1998; 158(6): 1907 - 1913. [Abstract] [Full Text] [PDF]

				J. Wang, H. Zheng, C.-C. Sung, K. K. Richter, and M. Hauer-Jensen Cellular Sources of Transforming Growth Factor-ß Isoforms in Early and Chronic Radiation Enteropathy Am. J. Pathol., November 1, 1998; 153(5): 1531 - 1540. [Abstract] [Full Text] [PDF]

				X. Huang, J. Wu, W. Zhu, R. Pytela, and D. Sheppard Expression of the Human Integrin beta 6 Subunit in Alveolar Type II Cells and Bronchiolar Epithelial Cells Reverses Lung Inflammation in beta 6 Knockout Mice Am. J. Respir. Cell Mol. Biol., October 1, 1998; 19(4): 636 - 642. [Abstract] [Full Text]