Authors
Ying Zhang, Yuzhuo Sun, Guangkui Xu, Yue Wu, Zhijun Shi, Zhuo Chang, Junjun Liu, Kaidan Pang, Siyu Liu, Han Wang, Weixin Rong, Zehua Shao, Xingqian Liu, Yu He, Yang Yan, Bin Zhou, Zuyi Yuan, Xu-Feng Zhang, Stefan Offermanns, Shengpeng Wang
Published in
Science (New York, N.Y.). Volume 393. Issue 6806. Pages eaef0825. Jul 02, 2026. Epub Jul 02, 2026.
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.
PMID:
42391361
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.
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