EGFR-mediated crosstalk between vascularendothelial cells and hepatocytes promotesPiezo1-dependent liver regeneration  

作　　者：Yuelei Hu Guifang Du Chao Li Rui Wang Juan Liu Yunfang Wang Jiahong Dong 

机构地区：[1]Department of Hepatobiliary and Pancreatic Surgery,The First Hospital of Jilin University,Jilin University,Changchun,Jilin 130021,China [2]Research Unit of Precision Hepatobiliary Surgery Paradigm,Chinese Academy of Medical Sciences,Beijing 102218,China [3]Hepatopancreatobiliary Center,Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University,Beijing 102218,China [4]Department of Biomedical Engineering,School of Medicine,Tsinghua University,Beijing 100084,China [5]Institute for Organ Transplant and Bionic Medicine,Tsinghua University,Beijing 100084,China [6]Clinical Translational Science Center,Beijing Tsinghua Changgung Hospital,Tsinghua University,Beijing 102218,China

出　　处：《Genes & Diseases》2025年第3期411-427,共17页基因与疾病(英文)

基　　金：supported by the National Key Research and Development Program of China(No.2022YFA1103400);the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5e056);the National Natural Science Foundation of China(No.81930119,92168207,32371477,82090051);the Precision Medicine Research Program of Tsinghua University(No.10001020612);the National High Level Hospital Clinical Research Funding(China)(No.2022-NHLHCRF-LX-03-0102).

摘　　要：Hepatocyte proliferation is essential for recovering liver function after injury. Inliver surgery, the mechanical stimulation induced by hemodynamic changes triggers vascularendothelial cells (VECs) to secrete large amounts of cytokines that enhance hepatocyte proliferation and play a pivotal role in liver regeneration (LR). Piezo1, a critical mechanosensory ionchannel, can detect and convert mechanical forces into chemical signals, importing externalstimuli into cells and triggering downstream biological effects. However, the precise role ofPiezo1 in VECs, especially in terms of mediating LR, remains unclear. Here, we report on a potential mechanism by which early changes in hepatic portal hemodynamics activate Piezo1 inVECs to promote hepatocyte proliferation during the process of LR induced by portal vein ligation in rats. In this LR model, hepatocyte proliferation is mainly distributed in zone 1 andzone 2 of liver lobules at 24e48 h after surgery, while only a small number of Ki67-positive hepatocytes were observed in zone 3. Activation of Piezo1 promotes increased secretion of epiregulin and amphiregulin from VECs via the PKC/ERK1/2 axis, further activating epidermalgrowth factor receptor (EGFR) and ERK1/2 signals in hepatocytes and promoting proliferation.In the liver lobules, the expression of EGFR in hepatocytes of zone 1 and zone 2 is significantlyhigher than that in zone 3. The EGFR inhibitor gefitinib inhibits LR by suppressing the proliferation of hepatocytes in the middle zone. These data provide a theoretical basis for the regulation of LR through chemical signals mediated by mechanical stimulation.

关 键 词：EGFR Hemodynamic changes Liver regeneration Piezo1 Vascular endothelial cells 

分 类 号：R657.3[医药卫生—外科学]