Zonated mechanosensing by PIEZO1 controls liver regeneration
Abstract
The liver exhibits a marked regenerative capacity organized through distinct zones, yet how tissue mechanics coordinate zonated proliferation remains elusive. We reveal that mechanical cues critically contribute to mouse liver regeneration in a highly region-specific manner through sensing by a subpopulation of mid-lobular hepatocytes, which are characterized by dipeptidyl peptidase-4 (DPP4) expression and represent the key proliferative pool of hepatocytes. PIEZO1 is a primary mechanosensor enriched in zone 2 DPP4 + hepatocytes that integrates biomechanical cues to drive liver regrowth by insulin-like growth factor binding protein 2 (IGFBP2). Genetic disruption of PIEZO1 restrains hepatocyte proliferation and compromises liver regeneration, whereas zonated PIEZO1 gain of function enhances proliferation and accelerates recovery. These findings reveal that DPP4 + mechanosensitive hepatocytes orchestrate liver regrowth through PIEZO1-mediated mechanosensing, establishing a link between tissue mechanics and liver regeneration.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (20)
Ying Zhang
Yuzhuo Sun
Department of Cardiovascular Surgery, Med-X Institute, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Guangkui Xu
Department of Engineering Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi’an Jiaotong University, Xi’an, China.
Yue Wu
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Zhijun Shi
Department of Engineering Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi’an Jiaotong University, Xi’an, China.
Zhuo Chang
Department of Engineering Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi’an Jiaotong University, Xi’an, China.
Junjun Liu
Techshake Biotechnology Co., Ltd., Xi’an, Shaanxi, China.
Kaidan Pang
Department of Cardiovascular Surgery, Med-X Institute, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Siyu Liu
Han Wang
Weixin Rong
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Zehua Shao
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Xingqian Liu
Department of Cardiovascular Surgery, Med-X Institute, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Yu He
Department of Cardiovascular Surgery, Med-X Institute, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Yang Yan
Department of Cardiovascular Surgery, Med-X Institute, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Bin Zhou
Zuyi Yuan
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Xu-Feng Zhang
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Stefan Offermanns
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Shengpeng Wang
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China.