Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive and fibrosing interstitial pneumonia of unknown cause. The main feature of IPF is a heterogeneous appearance with areas of sub-pleural fibrosis. However, the mechanism of sub-pleural fibrosis was poorly understood. In this study, our in vivo study revealed that pleural mesothelial cells (PMCs) migrated into lung parenchyma and localized alongside lung fibroblasts in sub-pleural area in mouse pulmonary fibrosis. Our in vitro study displayed that cultured-PMCs-medium induced lung fibroblasts transforming into myofibroblast, cultured-fibroblasts-medium promoted mesothelial-mesenchymal transition of PMCs. Furthermore, these changes in lung fibroblasts and PMCs were prevented by blocking TGF-β1/Smad2/3 signaling with SB431542. TGF-β1 neutralized antibody attenuated bleomycin-induced pulmonary fibrosis. Similar to TGF-β1/Smad2/3 signaling, wnt/β-catenin signaling was also activated in the process of PMCs crosstalk with lung fibroblasts. Moreover, inhibition of CD147 attenuated cultured-PMCs-medium induced collagen-I synthesis in lung fibroblasts. Blocking CD147 signaling also prevented bleomycin-induced pulmonary fibrosis. Our data indicated that crosstalk between PMC and lung fibroblast contributed to sub-pleural pulmonary fibrosis. TGF-β1, Wnt/β-catenin and CD147 signaling was involved in the underling mechanism.

特发性肺纤维化（IPF）是一种原因不明的慢性，进行性和纤维化间质性肺炎的特殊形式。IPF的主要特征是具有胸膜下纤维化区域的异质外观。但是，对胸膜下纤维化的机制了解甚少。在这项研究中，我们的体内研究表明，胸膜间皮细胞（PMC）迁移到肺实质中，并与小鼠肺纤维化的胸膜下区域的肺成纤维细胞一起定位。我们的体外研究表明，培养的PMCs-培养基诱导的肺成纤维细胞转化为肌纤维母细胞，培养的成纤维细胞-培养基促进PMCs的间皮-间质转化。此外，通过用SB431542阻断TGF-β1/ Smad2 / 3信号传导可防止肺成纤维细胞和PMC的这些变化。TGF-β1中和抗体减弱了博来霉素诱导的肺纤维化。与TGF-β1/ Smad2 / 3信号转导类似，在与肺成纤维细胞的PMC串扰过程中也激活了wnt /β-catenin信号转导。此外，抑制CD147减毒培养的PMCs-培养基可诱导肺成纤维细胞中的胶原蛋白I合成。阻断CD147信号传导还可以预防博来霉素诱导的肺纤维化。我们的数据表明，PMC和肺成纤维细胞之间的串扰导致胸膜下肺纤维化。TGF-β1，Wnt /β-catenin和CD147信号参与了基础机制。抑制CD147减毒培养的PMCs-培养基诱导的肺成纤维细胞中的胶原蛋白I合成。阻断CD147信号传导还可以预防博来霉素诱导的肺纤维化。我们的数据表明，PMC和肺成纤维细胞之间的串扰导致胸膜下肺纤维化。TGF-β1，Wnt /β-catenin和CD147信号参与了下标机制。抑制CD147减毒培养的PMCs-培养基诱导的肺成纤维细胞中的胶原蛋白I合成。阻断CD147信号传导还可以预防博来霉素诱导的肺纤维化。我们的数据表明，PMC和肺成纤维细胞之间的串扰导致胸膜下肺纤维化。TGF-β1，Wnt /β-catenin和CD147信号参与了基础机制。