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Puerarin protects fibroblasts against mechanical stretching injury through Nrf2/TGF-β1 signaling pathway

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Abstract

Introduction and hypothesis

Stress urinary incontinence (SUI) is the most common form of urinary incontinence in women, which affects women’s quality of life worldwide. Mechanical injury of the pelvic floor may disrupt the pelvic supportive tissues and connections via the remodeling of extracellular matrix (ECM), which is supposed to be one of the main pathological mechanisms of SUI.

Methods

The SUI mouse model was established using vaginal distension (VD). Leak point pressure (LPP), maximum cystometric capacity (MCC), collagen, Nrf2 and TGF-β1 in the anterior vaginal wall were measured in either wild-type or Nrf2-knockout (Nrf2-/-) female C57BL/6 mice with or without puerarin treatment. Then, the mechanical stretching (MS) loaded on L929 cells was generated by a four-point bending device. mTGF-β1 or LY2109761 (an inhibitor of TGF-β1) was used to verify the protective effect of puerarin after Nrf2 knockdown or overexpression.

Results

The collagen content of the anterior vaginal tissues in VD mice and LPP and MCC was decreased significantly. Besides, the expression levels of Nrf2, TGF-β1, collagen I and collagen III of MS group were downregulated in L929 cells. Puerarin pretreatment could reverse mechanical injury-induced collagen downregulation and Nrf2/TGF-β1 signaling inhibition. Moreover, both LY2109761 pretreatment and Nrf2 knockdown could attenuate the protective effect of puerarin in the mechanical injury-induced ECM remodeling, whereas exogenous TGF-β1 could counteract the effect of Nrf2 downregulation.

Conclusions

Puerarin protected fibroblasts from mechanical injury-induced ECM remodeling through the Nrf2/TGF-β1 signaling pathway. This might be a new strategy for the treatment of SUI.

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Data availability

The analyzed datasets generated during the study are available from the corresponding author on reasonable request.

Abbreviations

SUI:

stress urinary incontinence

ECM:

extracellular matrix

VD:

vaginal distension

LPP:

Leak point pressure

MCC:

maximum cystometric capacity

MS:

mechanical stretching

TGF-β1:

transforming growth factor β1

ROS:

reactive oxygen species.

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Acknowledgments

All authors thank all the teachers in the Department of Gynecology and Obstetrics and Central Laboratory, Renmin Hospital of Wuhan University, for their technical assistance.

Funding

The present study was financially supported by the Fundamental Research Funds for the Central Universities (grant number: 2042022kf1110), the National Key R&D Program of China (grant number: 2018YFC2002204 and 2021YFC2701302) and the National Natural Science Foundation of China (grant number: 81971364).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, People’s Republic of China

    Yang Li, Cheng Liu, Lian Yang, Lu Li & Li Hong

Authors
  1. Yang Li
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  2. Cheng Liu
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  3. Lian Yang
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  4. Lu Li
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  5. Li Hong
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Contributions

Yang Li: manuscript writing, investigation and data analysis; Cheng Liu and Lian Yang: development and design of methodology; Lu Li: data collection; Li Hong: project development.

Corresponding author

Correspondence to Li Hong.

Ethics declarations

The procedures of the animal study were approved by the ethics committee of the Institutional Animal Care and Use Committee of Renmin Hospital of Wuhan University (20161105).

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None.

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Li, Y., Liu, C., Yang, L. et al. Puerarin protects fibroblasts against mechanical stretching injury through Nrf2/TGF-β1 signaling pathway. Int Urogynecol J 33, 2565–2576 (2022). https://doi.org/10.1007/s00192-022-05325-z

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  • DOI: https://doi.org/10.1007/s00192-022-05325-z

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