1. UCN‐01 inhibits human IPF lung fibroblast pathological phenotypes and attenuates lung fibrosis induced by bleomycin injury
UCN‐01 inhibits human IPF lung fibroblast pathological phenotypes and attenuates lung fibrosis induced by bleomycin injury ASerum‐starved (48 h) IPF‐HLF (n = 5) were stimulated with 5% FCS and treated with UCN‐01 (10, , and 200 nM) or vehicle (DMSO) or left untreated, and cell proliferation was measured by BrdU incorporation after 24 h.BIPF‐HLF cells that were serum‐starved for 48 h and stimulated with TGF‐β1 (10 ng/ml) and treated with UCN‐01 (50 nM) or vehicle (DMSO) for 24 h. (B, left panel) Western blots of p‐FoxO3 (Thr32), p‐FoxO3 (Ser253), FoxO3, p‐AKT (Thr308), AKT, and GAPDH. (B, right panel) ICC of α‐SMA (red) and Col1a (green). TO‐PRO3 (blue) was used to label nuclei. Scale bar = 50 μm. Images are representative of n = 3.CScheme shows experimental setup.D–FLung function measurements of mice, (D) total lung capacity, (E) lung compliance, and (F) tissue resistance.GRepresentative H&E staining of whole left lung.HFibrotic score.Data information: Data are expressed as mean ± SEM. Data in (A) were analyzed using one‐way ANOVA, n.s. = not significant, ***P < 0.001 versus vehicle‐treated cells, §§§P < 0.001 versus 50 nM UCN‐01‐treated cells, ##P < 0.01 versus 100 nM UCN‐01‐treated cells. In (C–H): saline (n = 8 mice), bleomycin non‐treated (n = 7 mice), bleomycin vehicle‐treated (n = 8 mice), UCN‐01 5 mg/kg.bw (n = 10 mice), and UCN‐01 7.5 mg/kg.bw (n = 7 mice). In (D–F and H), data were analyzed using one‐way ANOVA, n.s. = not significant, *P < 0.05, **P < 0.01,***P < 0.001 versus vehicle‐treated mice.Source data are available online for this figure.
Hamza M Al‐Tamari et al. EMBO Mol Med. 2017;emmm
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