Exercise-induced circulating exosomes potentially prevent pelvic organ prolapse in clinical practice via inhibition of smooth muscle apoptosis

Yan Li; Min Kong; Jing Wang; Panpan Han; Nan Zhang; Xin Yang; Juanjuan Wang; Yanling Hu; Yinli Duo; Dan Liu

doi:10.1016/j.heliyon.2022.e12583

Exercise-induced circulating exosomes potentially prevent pelvic organ prolapse in clinical practice via inhibition of smooth muscle apoptosis

Heliyon. 2022 Dec 25;9(3):e12583. doi: 10.1016/j.heliyon.2022.e12583. eCollection 2023 Mar.

Authors

Yan Li¹, Min Kong², Jing Wang¹, Panpan Han², Nan Zhang², Xin Yang², Juanjuan Wang², Yanling Hu², Yinli Duo¹, Dan Liu¹

Affiliations

¹ General Hospital of Ningxia Medical University, Ning Xia, China.
² Ningxia Medical University, Ning Xia, China.

Abstract

Background: This study aimed to explore the potential mechanisms of exercise to prevent pelvic organ prolapse (POP) and search for diagnostic indictors for POP.

Methods: We used two clinical POP datasets with patients' information (GSE12852 and GSE53868), a dataset consisting of altered microRNA expression in circulating blood after exercise (GSE69717) for bioinformatic analysis and clinical diagnostic analysis, while a series of cellular experiments were conducted for preliminary mechanical validation.

Results: Our results show that AXUD1 is highly expressed in the smooth muscle of the ovary and is a key pathogenic gene in POP, while miR-133b is a key molecule in the regulation of POP by exercise-induced serum exosomes. The AUCs of AXUD1 for POP diagnosis were 0.842 and 0.840 in GSE12852 and GSE53868 respectively. At cut-off value = 9.627, the sensitivity and specificity of AXUD1 for predicating POP is 1.000 and 0.833 respectively for GSE53868, while at cut-off value = 3324.640, the sensitivity and specificity of AXUD1 for predicating POP is 0.941 and 0.812 separately for GSE12852. Analysis and experiments confirmed that miR-133b can directly regulate AXUD1. miR-133b mediated C2C12 myoblasts proliferation and inhibited hydrogen peroxide-induced apoptosis.

Conclusions: Our study proved that AXUD1 is a good clinical diagnostic indicator for POP and provided a theoretical basis for future prevention of POP through exercise and a potential target for intervention in muscle dysfunction.

Keywords: Apoptosis; Biomarker; Diagnostic; Exercise; Exosome; Pelvic organ prolapse; miRNA.