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. 2018 Dec 15;74(2):164–176. doi: 10.1136/thoraxjnl-2017-211440

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Transforming growth factor β-activated kinase 1 (TAK1) inhibition prevents tibialis anterior (TA) muscle atrophy in the monocrotaline (MCT) rat as well as preventing weight loss in some animals. (A) Right ventricular systolic pressure (RVSP) in control (● n=8), MCT (□ n=6) and MCT TAK1i (∆ n=6) treated rats (Kruskal-Wallis with Dunn’s correction, p=0.001). (B) Right ventricle/left ventricle plus septal (RV/LV+S) weight in control (● n=10), MCT (□ n=10) and MCT TAK1i (∆ n=9) treated rats (Kruskal-Wallis with Dunn’s correction, p<0.001). (C) Number of MCT animals growing and not growing at the end of the experiment in the MCT (n=10) and MCT TAK1i (n=9) groups (Fisher’s exact test, p=0.033). (D) TA weight in control (● n=10), MCT (□ n=10) and MCT TAK1i (∆ n=9) treated rats (one-way analysis of variance (ANOVA) with Bonferroni correction, p<0.001). (E) Fibre profiles of control (n=10), MCT (n=10) and MCT TAK1i (n=9) plotted as mean and SEM of proportion of fibres below the indicated fibre diameter in 5 µm increments (two-way ANOVA, p<0.001 for row, column and interaction, * and ** represent a significant difference between MCT and MCT TAK1 proportions at each 5 µm fibre intervals by Bonferroni). (F) Representative bright-field image of rat TA muscle tissue stained with H&E from which median fibre diameter was determined. (G) Log atrogin-1 mRNA expression in the TA of control (● n=10), MCT (□ n=10) and MCT TAK1i (∆ n=9) treated rats (Kruskal-Wallis with Dunn’s correction, p=0.018). (H) Log atrogin-1 mRNA expression in the TA of MCT-treated rats growing (● n=4) and not growing (□ n=15) at the end of the experiment (Mann-Whitney U test, p=0.032).

Inline graphic — Transforming growth factor β-activated kinase 1 (TAK1) inhibition prevents tibialis anterior (TA) muscle atrophy in the monocrotaline (MCT) rat as well as preventing weight loss in some animals. (A) Right ventricular systolic pressure (RVSP) in control (● n=8), MCT (□ n=6) and MCT TAK1i (∆ n=6) treated rats (Kruskal-Wallis with Dunn’s correction, p=0.001). (B) Right ventricle/left ventricle plus septal (RV/LV+S) weight in control (● n=10), MCT (□ n=10) and MCT TAK1i (∆ n=9) treated rats (Kruskal-Wallis with Dunn’s correction, p<0.001). (C) Number of MCT animals growing and not growing at the end of the experiment in the MCT (n=10) and MCT TAK1i (n=9) groups (Fisher’s exact test, p=0.033). (D) TA weight in control (● n=10), MCT (□ n=10) and MCT TAK1i (∆ n=9) treated rats (one-way analysis of variance (ANOVA) with Bonferroni correction, p<0.001). (E) Fibre profiles of control (n=10), MCT (n=10) and MCT TAK1i (n=9) plotted as mean and SEM of proportion of fibres below the indicated fibre diameter in 5 µm increments (two-way ANOVA, p<0.001 for row, column and interaction, * and ** represent a significant difference between MCT and MCT TAK1 proportions at each 5 µm fibre intervals by Bonferroni). (F) Representative bright-field image of rat TA muscle tissue stained with H&E from which median fibre diameter was determined. (G) Log atrogin-1 mRNA expression in the TA of control (● n=10), MCT (□ n=10) and MCT TAK1i (∆ n=9) treated rats (Kruskal-Wallis with Dunn’s correction, p=0.018). (H) Log atrogin-1 mRNA expression in the TA of MCT-treated rats growing (● n=4) and not growing (□ n=15) at the end of the experiment (Mann-Whitney U test, p=0.032).