Expression of Transforming Growth Factor-β Type I and Type II Receptors Is Altered in Rat Lungs Undergoing Bleomycin-Induced Pulmonary Fibrosis

• Published in: Experimental and molecular pathology 2000-10, Vol.69 (2), p.67-78
• Main Authors: Zhao, Yun, Shah, Deepti U.
• Format: Article
• Language: English
• Subjects: Activin Receptors, Type I; Animals; Antibiotics, Antineoplastic - toxicity; Biological and medical sciences; bleomycin; Bleomycin - toxicity; extracellular matrix; Gene Expression; Immunohistochemistry; Lung - drug effects; Lung - metabolism; lung injury; Medical sciences; Pneumology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Respiratory system : syndromes and miscellaneous diseases; RNA, Messenger - genetics; RNA, Messenger - metabolism; TGF-β; TGF-β type I receptor; TGF-β type II, receptor
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1006/exmp.2000.2319

Transforming growth factor-β (TGF-β) is a family of autocrine/paracrine/endocrine cytokines involved in controlling cell growth and extracellular matrix metabolism. TGF-β exerts its biological effects via binding to type I (TβRI) and type II (TβRII) receptors. To gain insight into the possible role of TGF-β receptors in the pathogenesis of pulmonary fibrosis, we investigated the expression of TGF-β receptors and their ligands in a bleomycin-induced model of pulmonary fibrosis. We found that the expression of both TβRI and TβRII was altered in rat lungs during pulmonary fibrosis induced by bleomycin. The increase in TβRI mRNA level was evident after 3 days of bleomycin administration, and TβRI mRNA continually increased for over 12 days after bleomycin instillation, whereas TβRII mRNA declined at day 3 post bleomycin instillation and then increased during the reparative phase of lung injury (days 8 and 12). The immunoreactivity for both TβRI and TβRII was detected in the cells of the interstitium, the epithelium, and the blood vessels of normal rat lungs. In bleomycin-induced pulmonary fibrosis, an extensive immunostaining for TβRI and TβRII was present in the cells at the sites of injury and active fibrosis. These results demonstrate that the expression of TGF-β type I and type II receptors was altered during pulmonary fibrosis, suggesting that the TGF-β signal transduction pathway may be involved in the pathogenesis of lung fibrosis.