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. 2024 Jul 16;9(16):e175290. doi: 10.1172/jci.insight.175290

Figure 2. Loss of Cebpa in AT2 cells promotes lung fibrotic response, impairs fibrosis resolution and lung repair.

Figure 2

(A) Schematic showing tamoxifen treatment and analysis timeline. (B–D) Representative immunostaining images (n = 3) of Cebpa expression, qPCR of Cebpa transcripts, and representative Western blot (n = 3) showing Cebpa expression from CebpaΔSftpc and Cebpafl/fl mice lungs, 4 weeks after tamoxifen treatment. Scale bar: 50 μM. (E and F) Weight change of CebpaΔSftpc (n = 14) and Cebpafl/fl (n = 12) mice, and survival curve of CebpaΔSftpc (n = 18) and Cebpafl/fl (n = 10) mice after first tamoxifen treatment, over a 26-week period. (G) Hydroxyproline assay showing collagen deposition from CebpaΔSftpc (n = 11) and Cebpafl/fl (n = 9) mice lungs 26 weeks after first tamoxifen treatment. (H and I) Representative Western blot and their quantification show fibronectin and α-SMA expression from CebpaΔSftpc and Cebpafl/fl mice lungs 26 weeks after tamoxifen treatment. (J) qPCR for profibrotic gene transcripts from CebpaΔSftpc and Cebpafl/fl mice lungs 26 weeks after first tamoxifen treatment. (K) Representative H&E staining showing lung sections from CebpaΔSftpc (n = 3) and Cebpafl/fl (n = 3) mice 26 weeks after first tamoxifen treatment. Scale bar: 100 μM. (L) Flow cytometry analysis of CD326+ cells from CebpaΔSftpc (n = 7) and Cebpafl/fl (n = 7) mice lungs 26 weeks after first tamoxifen treatment. (M) Schematic showing timeline for bleomycin treatment, tamoxifen treatment, and analysis. (N) Hydroxyproline assay from CebpaΔSftpc and Cebpafl/fl mice lungs at 4 and 5 weeks after bleomycin injury. (O) Hydroxyproline assay from CebpaΔSftpc and Cebpafl/fl mice lungs at 12 weeks after bleomycin injury. (P) Representative H&E staining showing lung sections from CebpaΔSftpc (n = 3) and Cebpafl/fl (n = 3) mice at 12 weeks after bleomycin injury. Scale bar: 200 μM. (Q and R) Survival curve and weight change of CebpaΔSftpc (n = 10) and Cebpafl/fl (n = 7) mice over a 12-week postbleomycin injury period. Data were analyzed using a Mann-Whitney U test. *P < 0.05, **P < 0.01, ****P < 0.0001.