2. Academic Validation
  3. High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating Piezo1

High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating Piezo1

  • Curr Med Sci. 2024 Jun 27. doi: 10.1007/s11596-024-2881-3.
Bo-Lang Deng 1,  Dong-Xu Lin 1,  Zhi-Peng Li 1,  Kang Li 1,  Peng-Yu Wei 1,  Chang-Cheng Luo 1,  Meng-Yang Zhang 2,  Quan Zhou 3,  Zheng-Long Yang 3,  Zhong Chen 4
Affiliations

Affiliations

  • 1 Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 3 School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.
  • 4 Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chenzhongtj@126.com.
PMID: 38926331 DOI: 10.1007/s11596-024-2881-3
Abstract

Objective: Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis.

Methods: Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH2O) or exposed to HHP (50 cmH2O or 100 cmH2O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism.

Results: The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors.

Conclusion: The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1.

Keywords

Piezo1; bladder outlet obstruction; fibrosis; high hydrostatic pressure.

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