Increased expression and altered localization of cathepsin Z are associated with progression to jaundice stage in primary biliary cholangitis.
Increased expression and altered localization of cathepsin Z are associated with progression to jaundice stage in primary biliary cholangitis.
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DOI：
10.1038/s41598-018-30146-w
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发表时间：
2018-08-07
影响因子：
4.6
通讯作者：
Nakamura M
中科院分区：
文献类型：
--
作者：
Aiba Y;Harada K;Ito M;Suematsu T;Aishima S;Hitomi Y;Nishida N;Kawashima M;Takatsuki M;Eguchi S;Shimoda S;Nakamura H;Komori A;Abiru S;Nagaoka S;Migita K;Yatsuhashi H;Tokunaga K;Nakamura M
我们最近的全基因组关联研究发现，NELFCD/CTSZ位点与日本人群原发性胆管炎（PBC）进展至黄疸阶段显著相关。本研究旨在探讨组织蛋白酶Z在PBC病因和病理中的作用。采用酶联免疫吸附试验测定血清组织蛋白酶Z水平。采用免疫印迹法和免疫组化法分析肝组织中组织蛋白酶Z的表达和定位。在PBC患者中，血清组织蛋白酶Z水平随着疾病进展而显著升高。此外，其水平与丙氨酸转氨酶、天冬氨酸转氨酶和总胆红素呈正相关，与血小板计数和白蛋白呈负相关。组织蛋白酶Z的表达显着增加，在PBC的后期阶段的肝细胞，其本地化从胆管周围的细胞质，其中一部分不再是共定位与内体/溶酶体囊泡改变。在其他胆汁淤积性肝病的终末期，包括脓毒症、阻塞性黄疸和Alagille综合征，也观察到组织蛋白酶Z表达的类似改变。我们的研究结果表明，肝细胞中组织蛋白酶Z的表达和定位的改变是PBC和其他胆汁淤积性肝病的特征，并与PBC的进展有关。
Our recent genome-wide association study found that the NELFCD/CTSZ locus was significantly associated with progression of primary biliary cholangitis (PBC) to jaundice stage in the Japanese population. In this study, we investigated the role of cathepsin Z in the etiology and pathology of PBC. Serum cathepsin Z levels were measured using enzyme-linked immunosorbent assay. The expression and localization of cathepsin Z in liver specimens were analyzed by western blotting and immunohistochemistry. In PBC patients, serum cathepsin Z levels were significantly increased with disease progression. In addition, its levels were positively correlated with alanine transaminase, aspartate transaminase and total bilirubin, and were negatively correlated with platelet count and albumin. Cathepsin Z expression was markedly increased in hepatocytes at later stages of PBC, and its localization was altered from the peri-bile canaliculus to the cytoplasm, where a fraction was no longer colocalized with endosomal/lysosomal vesicles. Similar altered expression of cathepsin Z was observed in end-stage of other cholestatic liver diseases including sepsis, obstructive jaundice, and Alagille syndrome. Our results indicate that altered expression and localization of cathepsin Z in hepatocytes are characteristic features of PBC and other cholestatic liver diseases, and are implicated in the progression of PBC.
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影响因子：
13.5
作者：
Nakamura, Minoru;Kondo, Hisayoshi;Ishibashi, Hiromi
通讯作者：
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作者：
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通讯作者：
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