Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis

• Published in: Molecular medicine reports Vol. 12; no. 1; pp. 1091 - 1097
• Main Authors: YANG, ZHIZHOU, SUN, ZHAORUI, LIU, HONGMEI, REN, YI, SHAO, DANBING, ZHANG, WEI, LIN, JINFENG, WOLFRAM, JOY, WANG, FENG, NIE, SHINAN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.07.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Actin; Actins - genetics; Actins - metabolism; Alveoli; Animals; Care and treatment; Cell adhesion & migration; Cell Differentiation - drug effects; Cell Line; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Collagen; Collagen - genetics; Collagen - metabolism; Connective tissue growth factor; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; Connective Tissue Growth Factor - pharmacology; Dose-Response Relationship, Drug; Edema; Extracellular matrix; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Gene Expression; Genetic aspects; Growth factors; Humans; Interstitial cells; Laboratories; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung diseases; Lungs; Male; Mortality; myofibroblast differentiation; Myofibroblasts - drug effects; Myofibroblasts - metabolism; Myofibroblasts - pathology; Paraquat; Paraquat - poisoning; Physiological aspects; Poisoning; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Rats; Rats, Sprague-Dawley; Risk factors; Rodents; Septum; Smooth muscle; Studies; China; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2015.3537

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.