Fig. 4.
NEU1-selective inhibition with C9-BA-DANA has a long-lasting therapeutic effect. (A–C) show findings in the acute injury model up to day 21 after bleomycin instillation, whereas (D and E) show findings in the chronic bleomycin challenge model. Mean ± S.D. values are shown in (A and D), whereas circles represent individual mice in (B, C, and E). In (A and D), asterisks indicate significant (P < 0.05) recovery of body weight in response to C9-BA-DANA treatment. In (B, C, and E), single asterisks indicate significant (P < 0.05) increases in collagen levels in bleomycin-challenged mice, and double asterisks indicate significant (P < 0.05) decreases induced by C9-BA-DANA therapy. (A) Time-dependent changes in total body weight after intratracheal bleomycin challenge on day 0 followed by therapy with daily intraperitoneal injections of PBS placebo (red) or indicated doses of C9-BA-DANA starting on day 7 (arrow). (B) Collagen protein in microgram per milligram of wet lung tissue measured based on hydroxyproline assay (QuickZyme) on day 14 after the bleomycin challenge with and without treatment with indicated doses of C9-BA-DANA. (C) Collagen protein in microgram per milligram of wet lung tissue measured based on hydroxyproline assay (QuickZyme) on day 21 after the bleomycin challenge with and without treatment indicated doses of C9-BA-DANA. (D) Time-dependent changes in total body weight in mice challenged with repeated intraperitoneal injections of bleomycin throughout the study period. Therapy with PBS placebo (red) or C9-BA-DANA (blue) was started on day 14 (arrow). Mice infused with PBS alone and treated with C9-BA-DANA are shown in green. (E) Collagen protein in microgram per milligram of wet lung tissue measured with the hydroxyproline assay (QuickZyme) on day 33, with and without treatment with C9-BA-DANA. Ctrl, control.