ABSTRACT: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are serious health concerns worldwide that require regular dialysis before a kidney transplant for a better quality of life. Due to aging and frailty, kidney dialysis patients are often limited in physical activity, which can lead to multiple health complications and sometimes result in patient death. Therefore, maintaining muscle health is crucial for kidney dialysis. We recently reported that personalized resistance-based exercise can improve frailty in kidney dialysis patients; however, the underlying molecular mechanisms by which resistance-based exercise improves muscle health are unknown. RNA-Seq analysis revealed that exercise promotes the expression of genes related to muscle stemness, regeneration, and differentiation. The IHC analysis revealed increased protein expression of stemness-associated proteins, including Lamin A/C, 5'-adenosine monophosphate-activated protein kinase (AMPK), paired box 7 (PAX7), vascular cell adhesion molecule 1 (VCAM-1), and Emerin. The IF analysis revealed increased protein expression of muscle differentiation markers, including myoblast determination protein 1 (MyoD), myosin heavy chain (MyoH), myogenin, desmin, dystrophin, and enolase 3. Furthermore, our study demonstrated that exercise upregulated proteins such as mitochondrial encoded cytochrome c oxidase III (MTCO3) and aconitase 2 (ACO2), which are involved in the oxidation of organic compounds and mitochondrial function in muscle. Moreover, we observed that exercise increased the protein expression of glucose transporter protein types 1 and 4 (GLUT1 and GLUT-4), glycogen synthase 1 and 2 (GYS1 and GYS2), and fatty acid binding protein 1 (FABP1), which participate in energy production through glucose uptake, glycogenesis, and fatty acid metabolism, respectively. These results suggest that personalized resistance-based muscle therapy in dialysis patients promotes the expression of genes and proteins associated with muscle stemness, regeneration, differentiation, and energy generation.
