研究团队发现，机械信号通过中小叶肝细胞亚群的感知，以高度区域特异性的方式对无主题肝再生起关键作用，中小叶肝细胞的特征是二肽基肽酶-4 （DPP4）的表达，代表了肝细胞的关键增殖池。PIEZO1是一种主要的机械传感器，富集于2区DPP4+肝细胞中，通过整合生物力学线索，通过胰岛素样生长因子结合蛋白2 （IGFBP2）驱动肝脏再生。PIEZO1的遗传破坏抑制肝细胞增殖并损害肝脏再生，而PIEZO1功能的分区增益增强增殖并加速恢复。这些发现表明，DPP4+机械敏感肝细胞通过PIEZO1介导的机械感知来协调肝脏再生，在组织力学和肝脏再生之间建立了联系。
据了解，肝脏表现出通过不同区域组织的显著再生能力，但组织力学如何协调分区增殖仍然是未知的。
附：英文原文
Title: Zonated mechanosensing by PIEZO1 controls liver regeneration
Author: 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
Issue&Volume: 2026-07-02
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.
DOI: aef0825
Source: https://www.science.org/doi/10.1126/science.aef0825