Farid Rola M, Abu-Zeid Riham M, El-Tawil Ahmed
Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2707-17. eCollection 2014.
Although accumulating data has implicated a role for the Apelinergic system in cirrhosis, the role of Apelin during different stages of fibrogenesis has not been clarified, whereas no studies have been conducted on its expression in human hepatocellular carcinoma (HCC). This study aimed to elucidate its role in hepatic remodelling and carcinogenesis.
Immunolocalization of Apelin was compared during different stages of HCV-induced liver disease (n=123).
Apelin level in hepatic stellate cells (HSC), portal fibroblast and endothelial cells was significantly elevated in F3 stage .In cirrhosis, the expression was markedly striking and extended as linear staining in the cirrhotic septa and proliferated capillaries. In liver cirrhosis with high grade dysplastic nodule (HGDN) group and liver cirrhosis with HCC group, Apelin was constantly expressed in the hepatocytes with the exemption of non-parenchymatous cells. Apelin gradually increased in HGDN, HCC grade-I and HCC grade II (P<0.0001). In contrast, Apelin gradually decreased in the cirrhosis adjacent to HGDN, HCC grade-I and HCC grade II (P<0.0001). The gradual incline in Apelin expression in dysplastic and malignant cells was paralleled by a decline in their adjacent cirrhotic liver (P=0.013).
In HCV chronic hepatitis, Apelin seems to manipulate the differentiation of HSC ending in hepatic remodelling. The uptake of Apelin from the stromal components by the epithelial cells may initiate the transformation of adjacent epithelial cells and supports the evolution and progression of dysplastic nodules and hepatocellular carcinoma. These findings could have both prognostic and therapeutic applications.
尽管越来越多的数据表明阿片肽系统在肝硬化中发挥作用，但阿片肽在肝纤维化不同阶段的作用尚未明确，且尚无关于其在人类肝细胞癌（HCC）中表达的研究。本研究旨在阐明其在肝脏重塑和致癌过程中的作用。
比较了丙型肝炎病毒（HCV）诱导的肝病不同阶段（n = 123）阿片肽的免疫定位情况。
在F3期，肝星状细胞（HSC）、门静脉成纤维细胞和内皮细胞中的阿片肽水平显著升高。在肝硬化中，其表达明显显著，并在肝硬化间隔和增生的毛细血管中呈线性染色扩展。在伴有高级别发育异常结节（HGDN）的肝硬化组和伴有HCC的肝硬化组中，除非实质细胞外，阿片肽在肝细胞中持续表达。阿片肽在HGDN、HCC I级和HCC II级中逐渐增加（P < 0.0001）。相比之下，在与HGDN、HCC I级和HCC II级相邻的肝硬化中，阿片肽逐渐减少（P < 0.0001）。发育异常和恶性细胞中阿片肽表达的逐渐升高与其相邻肝硬化肝脏中的表达下降平行（P = 0.013）。
在HCV慢性肝炎中，阿片肽似乎操纵肝星状细胞的分化，最终导致肝脏重塑。上皮细胞从基质成分中摄取阿片肽可能启动相邻上皮细胞的转化，并支持发育异常结节和肝细胞癌的演变和进展。这些发现可能具有预后和治疗应用价值。
