Lung volume and lung mechanics 21 days after left lobe pneumonectomy (PNX). The volume of total lungs and single lobes was determined by fluid displacement and corrected for body weight (43). (A) Mass-specific lung volume (ml/g). The right lung (RL) and total lung (RL+ left lung [LL]) volume of double transgenic mice without surgery (RL: 0.013 ± 0.001; RL+LL: 0.018 ± 0.002) and with sham surgery (RL: 0.014 ± 0.002; RL+LL: 0.019 ± 0.003) was determined (white column). At 21 days after left lung pneumonectomy, the volume of the right lung was determined in PNX animals (PNX: black column: 0.022 ± 0.002) in the absence of fibroblast growth factor (FGF) signaling (PNX + dominant-negative FGF receptor [dnFGFR], light gray column: 0.019 ± 0.004) and after daily injections of rosiglitazone (RZG) (PNX+RZG: dark gray column: 0.019 ± 0.005). *In all groups, mass specific volume of the right lung was significantly increased after surgery and was comparable to right and left lung mass before surgery. (B) Lung histology of SHAM, PNX, PNX+dnFGFR, and PNX+RZG was analyzed by H&E staining 21 days after pneumonectomy. SHAM and PNX animals show normal alveolar tissue. PNX+dnFGFR and PNX+RZG lungs demonstrate alveolar simplification. Scale bar, 50 μm. (C) Fractional airspace of the right lung was assessed by morphometric point intersection analysis. In SHAM-operated mice, the fractional airspace is 59.08 ± 0.25% (white column). In PNX, the fractional airspace is 59.03 ± 0.28% (black column). Compared with PNX lungs, fractional airspace in PNX+dnFGFR lungs is significantly increased to 64.99 ± 0.34% (light gray column). Compared with PNX lungs, fractional airspace in PNX+RZG lungs is significantly increased to 64.00 ± 0.24% (dark gray column). (D) Fractional airspace of the accessory lobe was assessed by morphometric point intersection analysis. In SHAM (white) and PNX (black) mice, the mean fractional airspace of the accessory lobe was not significantly changed (SHAM: 59.32 ± 0.31%; PNX: 59.52 ± 0.48%). In the presence of dnFGFR (light gray) or RZG (dark gray), the mean fractional airspace of the accessory lobe was significantly increased (PNX+dnFGFR: 65.85 ± 0.53%; PNX+RZG: 65.13 ± 0.29%). Comparisons among groups were made by one-way ANOVA using the Bonferroni’s multiple comparison test. Data are presented as mean ± SEM, with P < 0.05 considered significant (n ≥ 3 animals per group). (E and F) Lung mechanics were assessed 21 days after surgery. SHAM (white column), PNX (black column), PNX+dnFGFR (light gray column), and PNX+RZG (dark gray column). Lung mechanics in SHAM-, PNX-, and PNX+RZG-treated mice were comparable. Compared with PNX lungs, expression of dnFGFR after PNX surgery significantly increased tissue damping (E) and tissue elastance (F). Statistical differences were analyzed by Student’s t test (P < 0.05; n = 5 per group).