Ito Yoshiya, Hosono Kanako, Amano Hideki
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Front Cell Dev Biol. 2023 Apr 4;11:1171317. doi: 10.3389/fcell.2023.1171317. eCollection 2023.
The liver displays a remarkable regenerative capacity in response to acute liver injury. In addition to the proliferation of hepatocytes during liver regeneration, non-parenchymal cells, including liver macrophages, liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) play critical roles in liver repair and regeneration. Liver ischemia-reperfusion injury (IRI) is a major cause of increased liver damage during liver resection, transplantation, and trauma. Impaired liver repair increases postoperative morbidity and mortality of patients who underwent liver surgery. Successful liver repair and regeneration after liver IRI requires coordinated interplay and synergic actions between hepatic resident cells and recruited cell components. However, the underlying mechanisms of liver repair after liver IRI are not well understood. Recent technological advances have revealed the heterogeneity of each liver cell component in the steady state and diseased livers. In this review, we describe the progress in the biology of liver non-parenchymal cells obtained from novel technological advances. We address the functional role of each cell component in response to liver IRI and the interactions between diverse immune repertoires and non-hematopoietic cell populations during the course of liver repair after liver IRI. We also discuss how these findings can help in the design of novel therapeutic approaches. Growing insights into the cellular interactions during liver IRI would enhance the pathology of liver IRI understanding comprehensively and further develop the strategies for improvement of liver repair.
肝脏在应对急性肝损伤时表现出显著的再生能力。除了肝再生过程中肝细胞的增殖外,非实质细胞,包括肝巨噬细胞、肝窦内皮细胞(LSEC)和肝星状细胞(HSC)在肝脏修复和再生中发挥着关键作用。肝缺血再灌注损伤(IRI)是肝切除、移植和创伤期间肝损伤增加的主要原因。肝修复受损会增加接受肝脏手术患者的术后发病率和死亡率。肝IRI后成功的肝修复和再生需要肝驻留细胞和募集的细胞成分之间的协调相互作用和协同作用。然而,肝IRI后肝修复的潜在机制尚不完全清楚。最近的技术进步揭示了稳态和患病肝脏中每个肝细胞成分的异质性。在这篇综述中,我们描述了从新技术进步中获得的肝脏非实质细胞生物学的进展。我们阐述了每个细胞成分在应对肝IRI时的功能作用,以及肝IRI后肝修复过程中不同免疫细胞库与非造血细胞群体之间的相互作用。我们还讨论了这些发现如何有助于设计新的治疗方法。对肝IRI期间细胞相互作用的深入了解将全面增强对肝IRI病理学的理解,并进一步制定改善肝修复的策略。