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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Related Experiment Video

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High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating Piezo1.

Bo-Lang Deng1, Dong-Xu Lin1, Zhi-Peng Li1

  • 1Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Current Medical Science
|June 26, 2024
PubMed
Summary
This summary is machine-generated.

High hydrostatic pressure (HHP) activates Piezo1 channels, worsening bladder fibrosis by promoting fibroblast proliferation and pro-fibrotic factor expression. This suggests Piezo1 as a potential therapeutic target for bladder outlet obstruction complications.

Keywords:
Piezo1bladder outlet obstructionfibrosishigh hydrostatic pressure

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Area of Science:

  • Urology
  • Cell Biology
  • Biophysics

Background:

  • Bladder outlet obstruction (BOO) leads to chronic fibrosis and increased bladder pressure.
  • Piezo1 channels are mechanosensitive and respond to mechanical stimuli.

Purpose of the Study:

  • Investigate the effect of high hydrostatic pressure (HHP) on Piezo1 activity.
  • Determine the role of Piezo1 in the progression of bladder fibrosis.

Main Methods:

  • Assessed Piezo1 protein levels in rat bladder fibroblasts using immunofluorescence.
  • Exposed fibroblasts to HHP (50 or 100 cmH2O) or normal conditions.
  • Utilized Piezo1, YAP1, and ROCK1 agonists/inhibitors to elucidate mechanisms.

Main Results:

  • HHP increased Piezo1 expression, pro-fibrotic factors, and fibroblast proliferation.
  • Elevated Piezo1, YAP1, and ROCK1 levels and calcium influx correlated with increased pressure.
  • Piezo1 inhibition attenuated HHP-induced effects; Piezo1 activation mimicked these effects.

Conclusions:

  • High hydrostatic pressure may worsen bladder fibrosis by activating Piezo1.
  • Targeting Piezo1 could offer a therapeutic strategy for BOO-induced fibrosis.