tibialis: -5%, M. Results Repeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS-induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF- or synthetic GCs was prevented by GSK-3 inhibitors. Conclusions In a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy Metaxalone without affecting pulmonary inflammation. Resistance to inflammation- or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD. SB216763 or vehicle instillation. SB216763 is a selective GSK-3 inhibitor (3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione) (Tocris Cookson, Bristol, UK) and the LPS was derived from Fischers LSD test. The changes in body weight were tested using a mix-model design ANOVA. Mean value comparisons of data were tested non-parametrically, using the MannCWhitney U-test. A two-tailed probability value (p?Metaxalone GSK-3 inhibition helps prevent skeletal muscle mass atrophy induced by pulmonary swelling. (A) Body weight change of the guinea pigs during the experimental methods. (B) Effects of repeated LPS exposure and GSK-3 inhibition (SB216763) on skeletal muscle mass damp weights. (C) The dietary fiber cross-sectional area (CSA) of muscle mass materials in the extensor digitorum longus (EDL) muscle mass of the guinea pigs was identified from laminin-stained cross-sections. Representative laminin-stained (white) cross-sections of the same region within the EDL muscle mass for each experimental group (20X magnification, level pub?=?50?m). Histogram of quantitative analysis of the mean Type II cross-sectional area (CSA) (n?=?7 per group). (D) Dietary fiber size distribution curves of dietary fiber cross-sectional areas of materials in the EDL. All data demonstrated symbolize means SEM, n?=?9 animals per group. ***p?Rabbit Polyclonal to RNF111 adjustments in bodyweight were tested utilizing a mix-model style ANOVA. Mean worth evaluations of data had been examined non-parametrically, using the MannCWhitney U-test. A two-tailed possibility worth (p?