Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392 Giessen, Germany.
Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392 Giessen, Germany.
Cells. 2022 Jun 20;11(12):1973. doi: 10.3390/cells11121973.
Insulin-like growth factor (IGF) signaling controls the development and growth of many organs, including the lung. Loss of function of or its receptor impairs lung development and leads to neonatal respiratory distress in mice. Although many components of the IGF signaling pathway have shown to be dysregulated in idiopathic pulmonary fibrosis (IPF), the expression pattern of such components in different cellular compartments of the developing and/or fibrotic lung has been elusive. In this study, we provide a comprehensive transcriptional profile for such signaling components during embryonic lung development in mice, bleomycin-induced pulmonary fibrosis in mice and in human IPF lung explants. During late gestation, we found that is upregulated in parallel to downregulation in the lung mesenchyme. Lung tissues derived from bleomycin-treated mice and explanted IPF lungs revealed upregulation of IGF1 in parallel to downregulation of IGF1R, in addition to upregulation of several IGF binding proteins (IGFBPs) in lung fibrosis. Finally, treatment of IPF lung fibroblasts with recombinant IGF1 led to myogenic differentiation. Our data serve as a resource for the transcriptional profile of IGF signaling components and warrant further research on the involvement of this pathway in both lung development and pulmonary disease.
胰岛素样生长因子 (IGF) 信号通路控制着许多器官的发育和生长，包括肺。或其受体的功能丧失会损害肺的发育，并导致小鼠的新生儿呼吸窘迫。尽管 IGF 信号通路的许多成分在特发性肺纤维化 (IPF) 中被证明失调，但这些成分在发育中和/或纤维化肺的不同细胞区室中的表达模式仍难以捉摸。在这项研究中，我们提供了在小鼠胚胎肺发育、博来霉素诱导的小鼠肺纤维化和人 IPF 肺外植体中这种信号通路成分的综合转录谱。在妊娠后期，我们发现 在肺间质中与 的下调平行上调。来自博来霉素处理的小鼠的肺组织和外植的 IPF 肺揭示了 IGF1 的上调与 IGF1R 的下调平行，此外在肺纤维化中还上调了几种 IGF 结合蛋白 (IGFBPs)。最后，用重组 IGF1 处理 IPF 肺成纤维细胞导致成肌分化。我们的数据为 IGF 信号通路成分的转录谱提供了资源，并需要进一步研究该途径在肺发育和肺部疾病中的参与。
