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Copyright ©ERS Journals Ltd 2001
Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF
1 First Dept of Pathology and 2 Third Dept of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan, 3 Dept of Biochemistry and Molecular Dentistry, Okayama University Dental School, Japan
CORRESPONDENCE: T. Sawai, First Dept of Pathology, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka, 020-8505, Japan. Fax: 81 196519246
Keywords: connective tissue growth factor, idiopathic pulmonary fibrosis, immunohistochemistry, in situ hybridization, transforming growth factor-ß
Received: August 25, 2000
Accepted February 7, 2001
Supported by the Ministry of Education, Science and Culture, Japan.
Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor-ß. Previous studies have shown that both CTGF messenger ribonuclear acid (mRNA) and protein are expressed in renal fibrosis and bleomycin-induced pulmonary fibrosis in mice. The aim of the present study was to investigate the localization of CTGF protein and its mRNA expression in the fibrotic lung tissue of patients with idiopathic pulmonary fibrosis (IPF).
Using human fibrotic lung tissue obtained from eight autopsy cases and four biopsy cases with IPF, immunohistochemical staining, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were performed.
The cellular immunoreactivity for CTGF was markedly increased in the lung tissue of patients with IPF, compared to normal lungs. The immunolocalization of CTGF was confined predominantly to proliferating type II alveolar epithelial cells and activated fibroblasts. In the normal lung, type II alveolar epithelial cells stained for CTGF were sparsely distributed. CTGF mRNA was localized in proliferating type II alveolar epithelial cells and activated fibroblasts in the interstitium of fibrotic lung tissues. RT-PCR analysis showed that CTGF mRNA was expressed at a higher level in fibrotic lungs than in normal lungs.
In both an autocrine and a paracrine manner, type II alveolar epithelial cells and activated fibroblasts may play a critical role in pulmonary fibrosis by producing connective tissue growth factor which modulates fibroblast proliferation and extracellular matrix production.
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