Fgfr2b signaling in Alveolar Epithelial type II cells following pneumonectomy in mice

Abstract

Alveolar myofibroblasts are critical mesenchymal cells for the process of alveologenesis and the formation of the secondary septa. Fgf signaling through Fgfr2b ligands is required for the formation of the alveolar myofibroblasts during alveolar regeneration (Chen et al., 2012). However, the cells receiving such signaling and the mechanism of action of Fgf are still unclear. We showed that during embryonic development, alveolar epithelial progenitor cells respond to Fgf10/Fgfr2b signaling by producing Pdgfa, an essential growth factor for the formation of alveolar myofibroblasts (Ramasamy et al., 2007). We hypothesize that the alveolar epithelial type II cells (AECII) in the adult lung undergo Fgf signaling via the Fgfr2b receptor which is critical for the de novo formation of alveolar myofibroblasts. Moreover, this de novo signaling may be similar to the process happening during the embryonic stages of lung development. Sftpc CreERT2/+ ;Tomato flox/+ (control), Sftpc CreERT2/+ ;Tomato flox/+ ;Fgfr2b flox/flox or Sftpc CreERT2/+ ; Tomato flox/+ ; Fgf10 +/- (experimental) mice are fed with tamoxifen food for one week followed by a chase period with normal food. Sham or left lung pneumonectomy are carried out in control and experimental mice (d0) and the corresponding lungs are analyzed at d4, 7 and 14 during the process of de novo alveologenesis by stereology, IF, FACS (to sort Tomato-positive cells for gene arrays). Our results with the Sftpc CreERT2/+ ;Tomato flox/+ mice (PNX vs. SHAM) suggest that Fgf signaling is activated in AECII cells during PNX. Our ongoing experiments allow us to determine whether Fgfr2b signaling to the AECII cells in the adult lung plays a crucial role during de novo alveologenesis.