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

该资助申请是基于我们自上次提交以来最近接受出版的初步数据（Gupte等人，2009），表明在炎症或纤维化阶段期间肺中的成纤维细胞生长因子10（Fgf 10）过表达导致博来霉素诱导的纤维化的小鼠模型中的纤维化衰减。将要检验的中心假设是：FGF10在修复过程中控制肺上皮祖细胞的增殖和分化，从而影响肺纤维增生过程。提出了三个目标：目标1：目的2：确定FGF 10逆转非炎性肺纤维化模型中纤维增生事件的能力目的3：确定内源性FGFR 2b信号传导是否是导致小鼠纤维化减弱的修复过程所需的。

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.