FGF10 signaling in distal/alveolar epithelial progenitor cells - role in lung fibrosis

这项资助申请是基于我们最近接受发表的初步数据，自上次提交以来(Gupte等人，2009年)表明，在炎症或纤维化阶段，肺组织中成纤维细胞生长因子10(Fgf10)的过度表达导致博莱霉素诱导的纤维化小鼠模型的纤维化减弱。将被检验的中心假设是：FGF10在修复过程中控制肺上皮祖细胞的增殖和分化，从而影响肺纤维增殖过程。目的1：在炎症诱导的肺纤维化模型中，确定FGF10在损伤后修复过程中的作用。目的2：在非炎症性肺纤维化模型中，确定FGF10逆转纤维增殖事件的能力。目的3：确定内源性FGFR2b信号在导致小鼠纤维化减轻的修复过程中是否需要。

This grant application is based on our preliminary data recently accepted for publication since the previous submission (Gupte et al., 2009) indicating that Fibroblast growth factor 10 (Fgf10) overexpression in the lung during the inflammatory or fibrotic phase leads to fibrosis attenuation in a mouse model of bleomycin-induced fibrosis. The Central hypothesis that will be tested is: FGF10 controls the proliferation and differentiation of the pulmonary epithelial progenitor cells during the repair process, thereby affecting lung fibroproliferative processes. Three Aims are proposed: Aim 1: To determine the role of FGF10 during repair after injury in a model of inflammation-driven pulmonary fibrosis Aim 2: To determine the capability of FGF10 to reverse fibroproliferative events in a non- inflammatory lung fibrosis model Aim 3: To determine whether endogenous FGFR2b signaling is required for the repair process leading to attenuation of fibrosis in mice.