Gibert-Ramos Albert, Andrés-Rozas María, Pastó Raül, Alfaro-Retamero Pablo, Guixé-Muntet Sergi, Gracia-Sancho Jordi
Liver Vascular Biology Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
Clin Mol Hepatol. 2025 Jan;31(1):32-55. doi: 10.3350/cmh.2024.0734. Epub 2024 Oct 2.
The liver sinusoid, mainly composed of liver sinusoidal endothelial cells, hepatic macrophages and hepatic stellate cells, shapes the hepatic vasculature and is key to maintaining liver homeostasis and function. During chronic liver disease (CLD), the function of sinusoidal cells is impaired, being directly involved in the progression of liver fibrosis, cirrhosis, and main clinical complications including portal hypertension and hepatocellular carcinoma. In addition to their roles in liver diseases pathobiology, sinusoidal cells' paracrine communication or cross-talk is being studied as a mechanism of disease but also as a remarkable target for treatment. The aim of this review is to gather current knowledge of intercellular signalling in the hepatic sinusoid during the progression of liver disease. We summarise studies developed in pre-clinical models of CLD, especially emphasizing those pathways characterized in human-based clinically relevant models. Finally, we describe pharmacological treatments targeting sinusoidal communication as promising options to treat CLD and its clinical complications.
肝血窦主要由肝血窦内皮细胞、肝巨噬细胞和肝星状细胞组成，它塑造了肝脏血管系统，是维持肝脏内环境稳定和功能的关键。在慢性肝病（CLD）期间，血窦细胞的功能受损，直接参与肝纤维化、肝硬化以及包括门静脉高压和肝细胞癌在内的主要临床并发症的进展。除了在肝病病理生物学中的作用外，血窦细胞的旁分泌通讯或相互作用不仅作为一种疾病机制正在被研究，而且也是一个重要的治疗靶点。本综述的目的是收集有关肝病进展过程中肝血窦细胞间信号传导的当前知识。我们总结了在CLD临床前模型中开展的研究，特别强调了在基于人类的临床相关模型中所表征的那些途径。最后，我们描述了针对血窦通讯的药物治疗，将其作为治疗CLD及其临床并发症的有前景的选择。
