Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy
Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy
复制标题
充血性肝病小鼠模型中外周为主的肝纤维化和肿瘤分布
DOI：
10.1111/hepr.13866
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发表时间：
2022
影响因子：
4.2
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Kawai Hironari;Osawa Yosuke;et al.
目的充血性肝病常导致肝纤维化和肝细胞癌。影像学提供的临床证据表明，充血性肝病患者的肝脏硬度升高和肿瘤发生主要是在肝脏周围引起的。然而，肝硬度和肝纤维化的临床相关性尚不清楚，因为肝充血本身会增加充血性肝病的肝硬度。目前还不清楚是哪些因素造成了充血性肝病患者肿瘤发展的区域差异。为了回答这些问题，我们评估了宏观空间分布的肝纤维化和肿瘤的小鼠模型充血性hepatopathy.Methodschronic肝淤血诱导部分结扎肝上下腔静脉。通过组织学检查结果、基于激光显微切割（LMD）的qPCR和增强计算机断层扫描，评估肝上下腔静脉部分结扎小鼠中肝充血、纤维化和肿瘤的分布。进行基于LMD的RNA测序，以确定促进充血性hepatopathy.ResultsLiver肿瘤发展的因果因素，肝纤维化主要是在肝脏周围诱导，并与肝淤血分布共定位。在肝脏周围也诱发了肝肿瘤，其中发生了肝充血和纤维化。基于LMD的RNA测序显示上调细胞外基质/胶原纤维-，伤口愈合-，血管生成-，形态发生-，和细胞运动相关的信号通路在外周的肝脏相比，肝center.ConclusionsOur的研究结果显示，实验相关性的肝充血，纤维化和肿瘤的发展，充血性肝病，并可能提供重要的位置信息。应考虑在该小鼠模型中观察到的宏观区域差异来管理充血性肝病患者。
AimCongestive hepatopathy often leads to liver fibrosis and hepatocellular carcinoma. Imaging modalities provided clinical evidence that elevation of liver stiffness and tumor occurrence are mainly induced in the periphery of the liver in patients with congestive hepatopathy. However, clinical relevance of liver stiffness and liver fibrosis is unclear because liver congestion itself increases liver stiffness in congestive hepatopathy. It also unclear which factors configure such regional disparity of tumor development in patients with congestive hepatopathy. To answer these questions, we evaluated the macroscopic spatial distribution of liver fibrosis and tumors in the murine model of congestive hepatopathy.MethodsChronic liver congestion was induced by partial ligation of the suprahepatic inferior vena cava. Distribution of liver congestion, fibrosis, and tumors in partial ligation of the suprahepatic inferior vena cava mice were assessed by histological findings, laser microdissection (LMD)‐based qPCR and enhanced computed tomography. LMD‐based RNA‐sequencing was performed to identify causal factors that promote tumor development in congestive hepatopathy.ResultsLiver fibrosis was mainly induced in the periphery of the liver and co‐localized with distribution of liver congestion. Liver tumors were also induced in the periphery of the liver where liver congestion and fibrosis occurred. LMD‐based RNA‐sequencing revealed the upregulation of extracellular matrix/collagen fibril‐, wound healing‐, angiogenesis‐, morphogenesis‐, and cell motility‐related signaling pathways in periphery of liver compared with liver center.ConclusionsOur findings showed the experimental relevance of liver congestion, fibrosis, and tumor development in congestive hepatopathy, and may provide important locational information. Macroscopic regional disparity observed in this murine model should be considered to manage patients with congestive hepatopathy.
磁共振弹性图：一种新的技术，用于检测Fontan操作后肝纤维化和肝细胞癌。
影响因子：
8.9
作者：
Poterucha JT;Johnson JN;Qureshi MY;O'Leary PW;Kamath PS;Lennon RJ;Bonnichsen CR;Young PM;Venkatesh SK;Ehman RL;Gupta S;Smyrk TC;Dearani JA;Warnes CA;Cetta F
通讯作者：
Cetta F
影响因子：
3.5
作者：
Bryant, Timothy;Ahmad, Zaheer;Veldtman, Gruschen R.
通讯作者：
Veldtman, Gruschen R.