Biochemical and Biophysical Research Communications, Vol.509, No.4, 1021-1027, 2019
Neuromuscular electrical stimulation improves muscle atrophy induced by chronic hypoxia-hypercapnia through the MicroRNA-486/PTEN/FoxO1 pathway
Previous work has confirmed that the chronic hypoxia-hypercapnia (CHH) associated with chronic obstructive pulmonary disease contributes to the development of skeletal muscle atrophy. Neuromuscular Electrical Stimulation (NMES) has shown some efficacy when used as a treatment to reduce skeletal muscle atrophy. The present study focuses on the MicroRNA-486/PTEN/FoxO1 pathway with the goal of identifying its physiological role in skeletal muscle atrophy induced by CHH as well as its role during NMES treatment. To test this, 32 male Sprague Dawley rats were randomly divided into four groups. After completion of the disease modeling, gastrocnemius muscles were collected from all animals and cross-sectional areas of muscular fiber were observed and analyzed via H&E staining. MiR-486 expression was further assessed by qRT-PCR, and protein levels of TNF-alpha, PTEN, p-Akt, Akt, FoxO1, atrogin-1 and MuRF1 were measured by immunohistochemistry and western blotting. CSA, miR-486, and the ratio p-Akt/Akt were significantly reduced in the CHH group, while the levels of TNF-alpha, PTEN, FoxO1, atrogin-1, and MuRF1 were markedly increased. Importantly, these findings were reversed as a result of NMES. Thus, the MicroRNA-486/PTEN/FoxO1 pathway functions in muscle protein synthesis and degradation. New & Noteworthy: Our research provides a theoretical basis for the application of NMES as a means of improving muscle atrophy. Moreover, these therapeutic targets provide possible clues relevant to the treatment of amyotrophic diseases. (C) 2018 Published by Elsevier Inc.