Fig. 4.

Etv5 in AT2 cells is required for the repair of bleomycin-induced lung injury and for Kras-driven tumor initiation. (A) Scheme for the study of bleomycin-induced lung injury. Tam, tamoxifen. (B) Bleomycin-treated Sftpc^CreERT2/+Rosa^tdTomato/+ lung showing tdTomato expression (red) and BrdU incorporation (green). Arrowheads indicate tdTomato⁺ BrdU⁺ cells. (C) Lungs in B with tdTomato⁺ AT1 cells pseudocolored blue after being differentiated from AT2 cells by their lower staining intensity and elongated shape. (D) Quantification of tdTomato⁺ BrdU⁺ cells and relative numbers of AT1 versus AT2 cells. Data are shown as mean ± SEM; **P < 0.01, unpaired one-tailed Student's t test with Welch's correction; *P < 0.05, unpaired one-tailed Student's t test. AT1 and AT2 cells are distinguished as in C. (E) Immunostaining of a Kras^LSL/+ lung lesion 20 wk after infection with adenovirus expressing Cre. Arrowheads indicate Etv5⁺ cells adjacent to the lesions. AAH, atypical adenomatous hyperplasia. (F) Representative lung lesions at 20 wk after infection with adenovirus expressing Cre. The graph shows mean lesion numbers. Each dot represents one mouse. Bars indicate mean ± SEM. **P < 0.01, *P < 0.05 (Mann–Whitney test). (G) The graph indicates the extent to which the floxed Etv5 allele was retained in microdissected tumors from Kras^LSL/+ Etv5^fl/fl mice infected with adenovirus expressing Cre.