title: Electrical stimulation influences chronic intermittent hypoxia-hypercapnia induction of muscle fibre transformation by regulating the microRNA/Sox6 pathway.
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.
authors.affiliation: The Centre of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: The Centre of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: The Centre of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: The Centre of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shang
authors.affiliation: The Centre of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xianxun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: The Centre of Neurology and Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D006801:Humans; D006935:Hypercapnia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D048068:PPAR-beta / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C490916:Esrrg protein, mouse; D035683:MicroRNAs; D048068:PPAR-beta; D011960:Receptors, Estrogen; D055755:SOXD Transcription Factors; C095939:Sox6 protein, mouse