*2.6. GH Attenuates Muscle-Wasting Signaling and GH Resistance Pathways in CKD Mice*

Perturbations of metabolic pathways lead to skeletal muscle atrophy in the cachexia and sarcopenia. Proinflammatory cytokines induce the catabolic pathways in muscle [1,2]. Treatment of GH attenuated gastrocnemius mRNA expression of inflammatory cytokines (Il1β, Il6, and Tnfα) in CKD mice (Figure 5A–C). GH ameliorated muscle regeneration and myogenesis by decreasing the mRNA expression of negative regulators of skeletal muscle mass (Atrogin-1, Murf-1, Myostatin, and Soc2) while increasing the mRNA expression of promyogenic factors (MyoD, Myogenin, Pax-7, and IGF-I) in CKD mice (Figure 5D–G). In agreement with previous observations [14,15], we also found impaired JAK2/STAT5 signaling in gastrocnemius muscle in CKD mice (Figure 5L,M). GH normalized muscle protein content of phosphorylated JAK2 and STAT5 in CKD mice.

**Figure 5.** GH reduces muscle-wasting signaling pathways in CKD mice. CKD mice were fed ad libitum, whereas other mouse groups received an energy intake amount equal to that of CKD + Vehicle mice. By using qPCR, the expression of negative regulators of skeletal muscle mass (Il1β, Il6, Tnfα, Atrogin-1, Murf-1, and Socs2) as well as promyogenic factors (MyoD, Myogenin, Pax7, and IGF-I) in the gastrocnemius muscle was determined (**A**–**K**). In addition, by using the appropriate ELISA kits, the relative phosphorylated JAK2/total JAK2 ratio and the phosphorylated STAT5/total STAT5 ratio in the gastrocnemius muscle were evaluated (**L**,**M**). Results are analyzed and expressed as in Figure 2. Data are expressed as mean ± SEM. For comparison of the means between two groups, data were analyzed by Student's 2-tailed *t*-test. Posthoc analysis was performed with Tukey's test. Specific *p*-values are shown above the bar. ns signifies not significant, \* *p* < 0.05, \*\* *p* < 0.01.
