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Updated: Oct 15, 2025

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

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Shear stress-induced cellular senescence blunts liver regeneration through Notch-sirtuin 1-P21/P16 axis

Juan-Li Duan1, Bai Ruan1,2,3, Ping Song1

  • 1Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical University, Xi'an, China.

Hepatology (Baltimore, Md.)
|October 23, 2021
PubMed
Abstract

Insights

Cellular senescence, particularly in liver sinusoidal endothelial cells (LSECs), disrupts liver regeneration after partial hepatectomy (pHx). Activating Sirtuin 1 (Sirt1) reduces this senescence, promoting liver repair.

Area of Science:

  • Hepatology
  • Cellular Biology
  • Regenerative Medicine

Background:

  • Liver regeneration after partial hepatectomy (pHx) involves complex mechanisms.
  • Cellular senescence, a state of irreversible cell cycle arrest, is implicated in wound repair but its role in liver regeneration is not fully understood.

Purpose of the Study:

  • To elucidate the regulatory effects of cellular senescence on liver regeneration following pHx.
  • To investigate the role of Notch signaling and Sirtuin 1 (Sirt1) in LSEC senescence during liver regeneration.

Main Methods:

  • Mice underwent pHx and were analyzed 14 days post-surgery.
  • Investigated shear stress-induced endothelial nitric oxide synthase (eNOS) signaling and LSEC senescence.
  • Utilized Cdh5-CreERT NICeCA mice for Notch activation and a γ-secretase inhibitor (GSI) to block Notch.
  • Administered Sirt1 activator (SRT1720) to assess its effects on senescent LSECs and liver regeneration.

Main Results:

  • Incomplete sinusoid remodeling and accumulated senescent LSECs were observed 14 days post-pHx, impairing liver regeneration.
  • Notch activation in LSECs induced senescence and disrupted regeneration; blocking Notch with GSI promoted LSEC expansion.
  • Notch signaling inhibited Sirt1 transcription, leading to increased P53, P21, and P16.
  • Sirt1 activation by SRT1720 counteracted Notch-induced senescence by inhibiting P53, P21, and P16, promoting liver regeneration and sinusoid remodeling.

Conclusions:

  • Notch-driven LSEC senescence, induced by shear stress, impedes liver regeneration after pHx.
  • Sirt1 activation accelerates liver regeneration by mitigating Notch-driven LSEC senescence, offering a therapeutic target for liver injury.

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