Electrical stimulation influences chronic intermittent hypoxia-hypercapnia induction of muscle fibre transformation by regulating the microRNA/Sox6 pathway.

Shiyuan Huang,Jie Shen,Xiaotong Wang,Ping Shang,Lu Jin,Xianxun Jiang

doi:10.1038/srep26415

Shiyuan Huang, Jie Shen + Show 4 more

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https://doi.org/10.1038/srep26415

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Abstract

Chronic obstructive pulmonary disease can cause muscle fibre transformation due to chronic intermittent hypoxia-hypercapnia (CIHH). Studies have shown that high expression of Sox6 in muscle could suppress type-I fibres through downregulating the PPARβ (peroxisome proliferator-activated receptor β)/ERRγ (oestrogen-related receptor γ)/microRNA pathway. However, whether this pathway is involved in CIHH-induced muscle fibre transformation is unknown. Electrical stimulation (ES) is an effective approach to ameliorate muscle dysfunction. Here, we explored the effects of ES on CIHH-induced muscle fibre transformation and the microRNA/Sox6 pathway. After CIHH exposure, both the soleus (SOL) and gastrocnemius (GC) muscles showed decreased type-I fibres. The PPARβ/ERRγ/mir-499&208b (PEM, for GC) and PPARβ/mir-499&208b (PM, for SOL) signalling cascades were suppressed, followed by elevated Sox6 expression. Low frequency electrical stimulation (LFES) activated the PEM/PM pathway and enhanced type-I fibre numbers through suppressing Sox6 in SOL and GC. High frequency electrical stimulation (HFES) promoted type-I fibre expression through activating the PEM pathway in GC. Although PPARβ expression and type-I fibres were suppressed in SOL after HFES, no significant change was found in mir-499&208b/Sox6 expression. These results suggest that the microRNA/Sox6 pathway is disturbed after CIHH. Both low and high frequency electrical stimulations induce muscle fibre transformation partly through regulating the microRNA/Sox6 pathway.

Highlights

For example[9,10]
A previous study confirmed that mir-499 and mir-208b overexpression induces the upregulation of type-I fibre numbers, partly through suppressing Sox[613], a member of the Sox (Sry-related high motility group) family and a powerful slow fibre repressor, which may function as an architectural protein in transcription factor activation[14]
After chronic intermittent hypoxia-hypercapnia (CIHH) exposure, we found no significant change in cross-sectional area (CSA) in type-I fibres compared to the NC group

Summary

Introduction

For example[9,10]. Exercise endurance impairment occurs frequently in COPD patients and is mainly attributed to the fibre transformation from type-I to type-II11. Another study, focused on establishing the relationship between microRNA levels and exercise performance among COPD patients, found that decreased exercise tolerance was correlated with the downregulation of muscle mir-49918. These clues lead us to conjecture that the PPARβ/ERRγ/ microRNA/Sox[6] axis might be disturbed and is related to the slow fibre reduction caused by CIHH. We sought to explore the effects of electrical stimulation on type-I fibres across two different frequencies, with a specific focus on the PPARβ/ERRγ/microRNAs/Sox[6] axis in CIHH rats

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