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Small Extracellular Vesicles Secreted by Peri-urethral Tissues Regulate Fibroblast Function and Contribute to the Pathogenesis of Female Stress Urinary Incontinence

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Abstract

Objective

This study aimed to explore the existence of small extracellular vesicles (sEVs) in peri-urethral tissues and the role of abnormal expression of sEVs in the pathogenesis of female stress urinary incontinence (SUI).

Methods

sEVs were extracted from peri-urethral vaginal wall tissues using differential centrifugation and were observed by transmission electron microscopy (TEM). The number of sEVs and their protein contents were compared between SUI and control groups using nanoparticle tracking analysis (NTA) and bicinchoninic acid (BCA) protein assay. Fibroblasts were cultured separately with SUI (SsEVs group) and normal tissue sEVs (NsEVs group). Proliferation and migration of fibroblasts were compared between groups using CCK-8 and wound healing assays, respectively. Expression levels of collagen I and III were compared among blank control (BC), NsEVs, and SsEVs groups using real-time PCR. Protein mass spectrometry was used to test the differentially expressed proteins contained in sEVs between groups.

Results

sEVs were extracted and found under the electron microscope. There were significantly more sEVs extracted from the SUI group compared to the normal group. Fibroblasts showed increased proliferative and decreased migratory abilities, and expressed more collagen in the SsEVs group compared to the NsEVs and BC groups. Protein spectrum analysis demonstrated several differentially expressed targets, including components of microfibrils, elastin polymer, and anti-inflammatory factors.

Conclusion

sEVs were detected in the peri-urethral tissues. SUI tissues expressed more sEVs than control. The abnormal expression of sEVs and their protein contents may contribute to the pathogenesis and progression of SUI.

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Author notes

  1. Both authors contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China

    Ning Chen, Xiao-yan Sun, Zhi-chen Ding, Jia-qi Hu, Wen-juan Li, Li Zhan & Zhen-wei Xie

Authors
  1. Ning Chen
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  2. Xiao-yan Sun
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  3. Zhi-chen Ding
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  4. Jia-qi Hu
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  5. Wen-juan Li
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  6. Li Zhan
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  7. Zhen-wei Xie
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Corresponding author

Correspondence to Zhen-wei Xie.

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The authors declare that they have no competing interests.

Additional information

This research was supported by the Natural Science Foundation of Zhejiang Province (Nos. LQ22H040003 and LQ20H270019), and Medical Science and Technology Project of Zhejiang Province (No. 2021KY767).

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Chen, N., Sun, Xy., Ding, Zc. et al. Small Extracellular Vesicles Secreted by Peri-urethral Tissues Regulate Fibroblast Function and Contribute to the Pathogenesis of Female Stress Urinary Incontinence. CURR MED SCI 43, 803–810 (2023). https://doi.org/10.1007/s11596-023-2737-2

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  • DOI: https://doi.org/10.1007/s11596-023-2737-2

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