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Measurement of Vibration Detection Threshold and Tactile Spatial Acuity in Human Subjects
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Zonated mechanosensing by PIEZO1 controls liver regeneration.

Ying Zhang1, Yuzhuo Sun2, Guangkui Xu3

  • 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Science (New York, N.Y.)
|July 2, 2026
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Mechanical cues regulate liver regeneration. Mid-lobular hepatocytes expressing dipeptidyl peptidase-4 (DPP4) sense these cues via PIEZO1, driving liver regrowth by insulin-like growth factor binding protein 2 (IGFBP2).

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Area of Science:

  • Hepatology and regenerative medicine
  • Mechanobiology
  • Molecular and cellular biology

Background:

  • The liver's remarkable regenerative capacity is organized into distinct zones.
  • The precise mechanisms by which tissue mechanics coordinate zonated hepatocyte proliferation during regeneration are not well understood.

Purpose of the Study:

  • To investigate the role of mechanical cues in liver regeneration.
  • To identify the specific cell populations and molecular pathways involved in mechanosensing during liver regrowth.

Main Methods:

  • Utilized mouse models to study liver regeneration.
  • Employed genetic manipulation of PIEZO1 and dipeptidyl peptidase-4 (DPP4) expression.
  • Investigated the expression of DPP4 and PIEZO1 in different hepatocyte subpopulations.
  • Assessed the impact of PIEZO1 modulation on hepatocyte proliferation and liver regrowth.

Main Results:

  • Identified a subpopulation of mid-lobular hepatocytes, characterized by DPP4 expression, as the key proliferative pool.
  • Demonstrated that PIEZO1 is a primary mechanosensor enriched in zone 2 DPP4+ hepatocytes.
  • Showed that PIEZO1 integrates biomechanical cues to drive liver regrowth via insulin-like growth factor binding protein 2 (IGFBP2).
  • Found that genetic disruption of PIEZO1 impairs hepatocyte proliferation and liver regeneration.
  • Observed that enhanced PIEZO1 function accelerates liver recovery.

Conclusions:

  • DPP4+ mechanosensitive hepatocytes orchestrate liver regrowth through PIEZO1-mediated mechanosensing.
  • Established a direct link between tissue mechanics and liver regeneration.
  • Highlighted the region-specific contribution of mechanical cues to liver repair.