Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis
Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis
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DOI：
10.1111/hepr.13648
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发表时间：
2021-04-29
影响因子：
4.2
通讯作者：
Shirabe, Ken
中科院分区：
文献类型：
--
作者：
Gantumur, Dolgormaa;Harimoto, Norifumi;Shirabe, Ken
背景：Mac-2结合蛋白(M2BP)糖基化异构体(M2BPGi)是肝纤维化的血清标志物；M2BPGi是M2BP的糖基化形式。为了确定M2BP的来源，对肝细胞和肝星状细胞(HSCs)进行了研究。本研究旨在探讨肝纤维化组织中M2BP的来源。方法采用原位杂交和免疫组织化学方法，检测15例肝癌肝纤维化组织中M2BP的mRNA和M2BP的表达。用荧光原位杂交法检测M2BP和活化的HSC标志物αSMA mRNA的分布，用多色荧光免疫组织化学法检测M2BP、αSMA和CD68的蛋白定位。Kruskal-Wallis检验分析M2BP基因表达与血清纤维化标志物的关系。结果M2BP基因在纤维间隔和肝纤维化窦旁梭形细胞中均有表达。HSC标志物αSMA mRNA和M2BP mRNA共定位于梭形细胞，M2BP在蛋白水平表达于Kupffer细胞。M2BP基因表达与血清M2BPGi水平呈正相关。天冬氨酸氨基转移酶/血小板比值指数、纤维化-4、透明质酸、15min吲哚青绿滞留率与M2BP基因表达显著相关。结论肝星状细胞主要表达M2BP基因，但在M2BP水平未见转录，提示HSC可能产生M2BP并将其引入Kupffer细胞和血清。
Background Mac-2 binding protein (M2BP) glycosylated isomer (M2BPGi) is a serum marker of liver fibrosis; M2BPGi is a glycosylated form of M2BP. Hepatocytes and hepatic stellate cells (HSCs) have been studied to determine the source of M2BP. This study proposes to identify the origin of M2BP in fibrotic liver.Methods Using liver fibrosis tissue specimens from 15 patients with liver cancer, M2BP mRNA and M2BP were detected by in situ hybridization and immunohistochemistry, respectively. The expression levels of M2BP mRNA were evaluated with scores of 3, 2, and 1. Fluorescent in situ hybridization was carried out to evaluate the distribution of M2BP mRNA and the activated-HSC marker alpha SMA mRNA; multicolor fluorescent immunohistochemistry was used for protein localization of M2BP, alpha SMA, and CD68. The Kruskal-Wallis test analyzed the relationship between M2BP mRNA expression and existing serum fibrosis markers.Results M2BP mRNA was expressed in spindle-shaped cells along the fibrous septa and in the perisinusoidal area of the fibrotic liver. The HSC markers alpha SMA mRNA and M2BP mRNA were colocalized in the spindle-shaped cells; on the protein level, M2BP was expressed in Kupffer cells. M2BP mRNA expression was positively correlated with serum M2BPGi levels. Aspartate transaminase-to-platelet ratio index, Fibrosis-4, hyaluronic acid, and the 15-minute indocyanine green retention rate were significantly correlated with M2BP mRNA expression.Conclusions M2BP mRNA transcription in fibrotic liver was primarily observed in HSCs but not at the M2BP level, which suggests that HSCs might produce and introduce M2BP to Kupffer cells and serum.