title: Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.
abstract: 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.
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Zhizhou
authors: Z
authors: Yang
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Zhaorui
authors: Z
authors: Sun
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Hongmei
authors: H
authors: Liu
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Yi
authors: Y
authors: Ren
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Danbing
authors: D
authors: Shao
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Jinfeng
authors: J
authors: Lin
authors: CAS Key Laboratory for Biomedial Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing 100190, P.R. China.
authors: Joy
authors: J
authors: Wolfram
authors: Department of Gastroenterology, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai 200072, P.R. China.
authors: Feng
authors: F
authors: Wang
authors: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Shinan
authors: S
authors: Nie
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010269:Paraquat / Q000506:poisoning*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D003094:Collagen; D055513:Connective Tissue Growth Factor; D010269:Paraquat; C526317:CCN2 protein, human; C526316:CCN2 protein, rat; C498862:Acta2 protein, rat