Connective-Tissue Growth Factor Contributes to TGF-b1-induced Lung Fibrosis

Toyoshi Yanagihara, Kazuya Tsubouchi, Mahsa Gholiof, Sy Giin Chong, Kenneth E. Lipson, Quan Zhou, Ciaran Scallan, Chandak Upagupta, Jussi Tikkanen, Shaf Keshavjee, Kjetil Ask, Martin R.J. Kolb

    Research output: Contribution to journalArticlepeer-review

    42 Citations (Scopus)


    Idiopathic pulmonary fibrosis is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts and in the lung. Connective-tissue growth factor (CTGF) exacerbates pulmonary fibrosis in radiation-induced lung fibrosis, and in this study, we demonstrate upregulation of CTGF in a rat lung fibrosis model induced by an adenovirus vector encoding active TGF-b1 (AdTGF-b1). We show that CTGF is also upregulated in patients with idiopathic pulmonary fibrosis. Expression of CTGF was upregulated in vascular smooth muscle cells cultured from fibrotic lungs on Days 7 and 14 as well as endothelial cells sorted from fibrotic lungs on Days 14 and 28. These findings suggest contributions of different cells in maintaining the fibrotic phenotype during fibrogenesis. Treatment of fibroblasts with recombinant CTGF along with TGF-b increases profibrotic markers in fibroblasts, confirming the synergistic effect of recombinant CTGF with TGF-b in inducing pulmonary fibrosis. Also, the fibrotic extracellular matrix upregulated CTGF expression, compared with the normal extracellular matrix, suggesting that not only profibrotic mediators but also a profibrotic environment contributes to fibrogenesis. We also showed that pamrevlumab, a CTGF inhibitory antibody, partially attenuates fibrosis in the model. These results suggest that pamrevlumab could be an option for treatment of pulmonary fibrosis.

    Original languageEnglish
    Pages (from-to)260-270
    Number of pages11
    JournalAmerican journal of respiratory cell and molecular biology
    Issue number3
    Publication statusPublished - Mar 2022

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Pulmonary and Respiratory Medicine
    • Clinical Biochemistry
    • Cell Biology


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