肝星状细胞
肝细胞
平衡
细胞生物学
肝再生
生物
旁分泌信号
自分泌信号
信号转导
内分泌学
受体
再生(生物学)
生物化学
体外
作者
Vincent Quoc‐Huy Trinh,Ting-Fang Lee,Sara Lemoinne,Kevin C. Ray,Maria D. Ybanez,Takuma Tsuchida,James K Carter,Judith Agudo,Brian D. Brown,Kemal M. Akat,Scott L. Friedman,Youngmin A. Lee
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2023-05-30
卷期号:16 (787)
被引量:5
标识
DOI:10.1126/scisignal.adf6696
摘要
Organ size is maintained by the controlled proliferation of distinct cell populations. In the mouse liver, hepatocytes in the midlobular zone that are positive for cyclin D1 (CCND1) repopulate the parenchyma at a constant rate to preserve liver mass. Here, we investigated how hepatocyte proliferation is supported by hepatic stellate cells (HSCs), pericytes that are in close proximity to hepatocytes. We used T cells to ablate nearly all HSCs in the murine liver, enabling the unbiased characterization of HSC functions. In the normal liver, complete loss of HSCs persisted for up to 10 weeks and caused a gradual reduction in liver mass and in the number of CCND1+ hepatocytes. We identified neurotrophin-3 (Ntf-3) as an HSC-produced factor that induced the proliferation of midlobular hepatocytes through the activation of tropomyosin receptor kinase B (TrkB). Treating HSC-depleted mice with Ntf-3 restored CCND1+ hepatocytes in the midlobular region and increased liver mass. These findings establish that HSCs form the mitogenic niche for midlobular hepatocytes and identify Ntf-3 as a hepatocyte growth factor.
科研通智能强力驱动
Strongly Powered by AbleSci AI