title: Estrogen/ERR-α signaling axis is associated with fiber-type conversion of upper airway muscles in patients with obstructive sleep apnea hypopnea syndrome.
abstract: Estrogen is related with the low morbidity associated with obstructive sleep apnea hypopnea syndrome (OSAS) in women, but the underlying mechanisms remain largely unknown. In this study, we examined the relationship between OSAS and estrogen related receptor-α (ERR-α). We found that the expression levels of ERR-α and Myh7 were both downregulated in palatopharyngeal tissues from OSAS patients. In addition, we report that ERR-α is dynamically expressed during differentiation of C2C12 myoblasts. Knockdown of ERR-α via instant siRNA resulted in reduced expression of Myh7, but not Myh4. Furthermore, differentiation of C2C12 cells under 3% chronic intermittent hypoxia, a model resembling human OSAS, was impaired and accompanied by a obvious reduction in Myh7 expression levels. Moreover, activation of ERR-α with 17β-estradiol (E2) increased the expression of Myh7, whereas pretreatment with the ERR-α antagonist XCT790 reversed the E2-induced slow fiber-type switch. A rat ovariectomy model also demonstrated the switch to fast fiber type. Collectively, our findings suggest that ERR-α is involved in estrogen-mediated OSAS by regulating Myhc-slow expression. The present study illustrates an important role of the estrogen/ERR-α axis in the pathogenesis of OSAS, and may represent an attractive therapeutic target, especially in postmenopausal women.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Neurobiology, Southern Medical University, Guangzhou, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Guan
authors.affiliation: Department of Neurobiology, Southern Medical University, Guangzhou, China.
authors.forename: S J
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Anatamy, Southern Medical University, Guangzhou, China.
authors.forename: T T
authors.initials: TT
authors.lastname: Hu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Peng
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: F P
authors.initials: FP
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: B L
authors.initials: BL
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: X P
authors.initials: XP
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002460:Cell Line; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology; D032446:Myoblasts / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D010614:Pharynx / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020181:Sleep Apnea, Obstructive / Q000378:metabolism* / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; C501641:MYH7 protein, human; D004958:Estradiol; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains