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Direct mechanical exposure initiates hepatocyte proliferation
Wang Li1,2, Yi Wu1,2, Wenhui Hu1
1Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
JHEP Reports : Innovation in Hepatology
|November 3, 2023
Summary
Mechanical forces, specifically interstitial flow, stimulate liver regeneration by promoting hepatocyte proliferation. This process involves β1 integrin and YAP signaling, offering a new model for in vitro liver cell expansion.
Area of Science:
- Hepatology and regenerative medicine
- Mechanobiology
- Cell signaling
Background:
- Liver regeneration relies on paracrine signaling between liver sinusoid endothelial cells and hepatocytes in response to mechanical stimuli.
- Interstitial flow in the space of Disse influences hepatocyte responses after partial hepatectomy, but mechanisms are unclear.
Purpose of the Study:
- To investigate the role of interstitial flow and shear stress in stimulating hepatocyte proliferation.
- To elucidate the underlying molecular pathways involved in flow-induced hepatocyte regeneration.
Main Methods:
- Ex vivo mouse liver perfusion to assess interstitial flow effects on hepatocyte proliferation.
- In vitro exposure of isolated hepatocytes to controlled shear stresses.
- Knockdown and inhibition of mechanosensitive proteins to identify signaling pathways.
Main Results:
- Increased interstitial flow was visualized, and hepatocyte regeneration was confirmed ex vivo.
- In vitro studies demonstrated that fluid flow directly stimulates hepatocyte proliferation in a duration- and amplitude-dependent manner.
- Flow enhanced β1 integrin expression and YAP nuclear translocation via the Hippo pathway, promoting cell cycle re-entry.
Conclusions:
- Direct exposure to interstitial flow or shear stress initiates hepatocyte proliferation, providing new insights into mechanical forces in liver regeneration.
- Shear flow-induced hepatocyte proliferation occurs through β1 integrin-YAP mechanotransductive pathways.
- This study presents a valuable model for potentiating hepatocyte expansion in vitro using mechanical forces.
