Small extracellular vesicles secreted by vaginal fibroblasts exert inhibitory effect in female stress urinary incontinence through regulating the function of fibroblasts.

Xiaoyan Sun,Xiaoyong Li,Huimin Zhu,Zhenwei Xie,Wenhua Li,Wenjuan Li,Li Zhao,Yi Cao

doi:10.1371/journal.pone.0249977

Xiaoyan Sun, Xiaoyong Li + Show 6 more

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https://doi.org/10.1371/journal.pone.0249977

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Abstract

Stress urinary incontinence (SUI) is a common condition in women and associated with extra-cellular matrix (ECM) reconstruction, which is mainly regulated by fibroblasts. However, the underlying mechanism remains obscure. Small extracellular vesicles (sEVs) play fundamental biological roles in various cellular functions. Some studies suggested that the sEVs were involved in the metabolism of ECM and the function of fibroblasts. The purpose of our study was to investigate the effect of sEVs secreted by vaginal fibroblasts on the pathogenesis of SUI. We showed that the fibroblasts of female anterior vaginal wall secreted sEVs. Moreover, fibroblasts of females with SUI had significantly elevated secretion of sEVs. The collagen contents, proliferation and migration capacity of fibroblasts were decreased when fibroblasts were co-cultured with fibroblasts-derived sEVs (fibroblast-sEVs) from SUI patients. Proteomic analysis revealed that fibroblast-sEVs contained various differentially expressed proteins including TIMP2, TGF-β and ABCC4, which were involved in signaling pathways of fibroblasts regulation. Therefore, we suggested that fibroblast-sEVs contributed to the pathogenesis of SUI through various proteins including TIMP2, TGF-β and ABCC4.

Highlights

Stress urinary incontinence (SUI) is defined as the involuntary leakage of urine during laughing, coughing, sneezing or physical exercise
The characteristics of fibroblast-Small extracellular vesicles (sEVs) had been published as a conference paper previously [22], manifesting the isolated particles had characteristic of fibroblast-sEVs which were suitable for following experiments
By Using BCA protein quantification and nanoparticle size tracking analyzer (NTA) methods, we evaluated the quantity of sEVs from subjects with SUI and non-SUI

Summary

Introduction

Stress urinary incontinence (SUI) is defined as the involuntary leakage of urine during laughing, coughing, sneezing or physical exercise. Many studies suggested that the development of SUI was accompanied by fibroblast dysfunction [3,4,5,6]. The bladder and urethra were kept in place by the anterior vaginal wall which consisted of a dense extra-cellular matrix (ECM) regulated by fibroblasts [6]. Fibroblasts remodeled their surrounding matrix and maintained tissue homeostasis by altering own functional activity and producing active substance, which was involved in soft tissue repair [6]

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