Estrogen/ERR-α signaling axis is associated with fiber-type conversion of upper airway muscles in patients with obstructive sleep apnea hypopnea syndrome.

H H Chen,J Lu,F P Zhao,X P Li,Z S Xie,S J Li,T T Hu,X Xu,X H Peng,Y F Guan,F Wang,X Liu,B L Yu

doi:10.1038/srep27088

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.

Highlights

Effects via modulation of MAP kinase signaling[13]. It is unclear whether ERR-αmediates the conversion of fiber types of UA muscle in obstructive sleep apnea hypopnea syndrome (OSAS) patients or contributes to pharyngeal collapse
We found that ERR-αand Myh[7] were both downregulated in tissues from OSAS patients compared to tissues from control patients (Fig. 1a,b)
We observed that fiber type IIx was increased, whereas fiber type I was decreased in tissues from OSAS patients compared with those from control patients (Fig. 1e)

Summary

Introduction

Effects via modulation of MAP kinase signaling[13]. It is unclear whether ERR-αmediates the conversion of fiber types of UA muscle in OSAS patients or contributes to pharyngeal collapse. We investigated the relationship between ERR-αand OSAS by examining the expression of ERR-αand Myh[7] in male patients with OSAS. We explored the the possible mechanisms underlying fiber-type switch in OSAS patients. A clearer understanding of how sex hormones influence the morbidity associated with OSAS could enable therapeutic interventions for high-risk female patients experiencing postmenopause

Methods

Results

Discussion

Conclusion