Figure 5. Sftpc^I73T expression induces diffuse parenchymal lung remodeling, restrictive lung physiology, and AT2 cell expansion.

H&E sections of control (I^ER-SP-C^I73T/I73TFlp^–/–) (A and B) and inducible I^ER-SP-C^I73T/I73TFlp^+/– (C and D) mice 6 weeks after 300 mg/kg iTAM showing extensive parenchymal (D, box) and subpleural remodeling (C, arrowheads). On higher power, focal consolidations with features of fibroblastic foci are identified (D, arrow). (E) Double-label immunohistochemistry of 6-week iTAM-treated I^ER-SP-C^I73T/I73TFlp^+/– lungs showing focal airspace enlargement lined by proSP-C AT2 cells (arrows) with adjacent α-SMA–positive myofibroblasts (dashed circle). Scale bars: 50 μm (left), 20 μm (right). (F) MicroCT scans of I^ER-SP-C^I73T/I73TFlp^–/– and I^ER-SP-C^I73T/I73TFlp^+/+ mice at 6 weeks after 200 mg/kg tamoxifen. (G) Control (I^ER-SP-C^I73T/I73TFlp^–/–) and I^ER-SP-C^I73T/I73TFlp^+/– mice 4 weeks after 250–300 mg/kg tamoxifen administration were subjected to pulmonary function testing. Pooled flow volume loops (left) from each cohort (n = 12) and calculated static compliance (Cst, right) demonstrating restrictive physiology. *P < 0.05 versus I^ER-SP-C^I73T/I73TFlp^–/– control. (H) Representative ×20 fluorescence micrograph from I^ER-SP-C^I73T/I73TFlp^+/– lung 7 days after iTAM induction stained with anti-HA (red) and Ki-67 (green). (I and J) Sections were analyzed by manual counting. Dot plots with mean ± SEM are shown as the absolute number of HA⁺ cells per ×20 field (I) or percent of double-positive Ki-67⁺HA⁺ cells (J). *P < 0.05 versus I^ER-SP-C^I73T/I73TFlp^–/– control by 1-way ANOVA. (K) Sections double stained for α-HA and α–cleaved caspase-3 (Cl Casp-3) were manually counted as for I and J. Dot plots of double-positive (Cl Casp-3/HA⁺) cells expressed as a percentage of total HA⁺ AT2 cells are shown with mean and SEM. NS: P > 0.05 versus I^ER-SP-C^I73T/I73TFlp^–/– control by 1-way ANOVA.