Mechanical stretch triggers rapid epithelial cell division through Piezo1.

Area of Science:

• Cell biology
• Biophysics
• Tissue homeostasis

Background:

• Epithelial cells form vital barriers but have high turnover rates.
• Maintaining epithelial barrier integrity requires balancing cell division and death.
• The mechanisms controlling cell division to match cell death remain unclear.

Purpose of the Study:

• To investigate how mechanical forces regulate epithelial cell division and death.
• To elucidate the role of the Piezo1 channel in epithelial homeostasis.
• To understand how different mechanical cues lead to distinct cellular outcomes.

Main Methods:

• Experimental mechanical stretching of mammalian epithelia.
• Analysis of cell division and extrusion rates.
• Investigation of Piezo1 channel localization and activation.
• Assessment of cell cycle progression markers (e.g., cyclin B) and signaling pathways (e.g., ERK1/2 phosphorylation).

Main Results:

• Mechanical stretch rapidly stimulates epithelial cell division via Piezo1 activation.
• Stretch triggers G2-phase cells to divide by activating calcium-dependent ERK1/2 phosphorylation and cyclin B transcription.
• Cell crowding induces cell extrusion, also requiring Piezo1.
• Piezo1 localization differs: plasma membrane/cytoplasm in dividing cells, cytoplasmic aggregates in extruding cells.

Conclusions:

• Mechanical forces, sensed by Piezo1, are critical regulators of epithelial cell number.
• Stretch promotes cell division, while crowding induces cell extrusion, maintaining tissue homeostasis.
• Differential Piezo1 localization and activation dictate distinct cellular responses to mechanical cues.