原发性硬化性胆管炎患者胆管上皮细胞中 TNFRSF14 和 LIGHT 的表达增加。

Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.

机构信息

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Division of Gastroenterology, The Institute of Medical Science, Asahi Life Foundation, 2-2-6 Bakurocho, Chuo-ku, Tokyo, 103-0002, Japan.

出版信息

Dig Liver Dis. 2024 Feb;56(2):305-311. doi: 10.1016/j.dld.2023.08.057. Epub 2023 Sep 17.

DOI:10.1016/j.dld.2023.08.057

PMID:37722959

Abstract

BACKGROUND AND AIMS

There is a lack of biliary epithelial molecular markers for primary sclerosing cholangitis (PSC). We analyzed candidates from disease susceptibility genes identified in recent genome-wide association studies (GWAS).

METHODS

Expression levels of GWAS genes were analyzed in archival liver tissues of patients with PSC and controls. Immunohistochemical analysis was performed to evaluate expression levels in the biliary epithelia of PSC (N = 45) and controls (N = 12). Samples from patients with primary biliary cholangitis (PBC) were used as disease controls (N = 20).

RESULTS

Hepatic expression levels of ATXN2, HHEX, PRDX5, MST1, and TNFRSF14 were significantly altered in the PSC group. We focused on the immune-related receptor, TNFRSF14. Immunohistochemistry revealed that high expression of TNFRSF14 in biliary epithelial cells was observed only in the PSC group. In addition, the expression of LIGHT, which encodes a TNFRSF14-activating ligand, was increased in PSC liver. Immunohistochemistry showed that high expression of LIGHT was more common in PSC biliary epithelia (53%) than in the PBC (15%) or control (0%) groups; moreover, it was positively associated with fibrotic progression, although it was not an independent prognostic factor.

CONCLUSIONS

TNFRSF14 and LIGHT are promising candidate markers for PSC.

摘要

背景和目的

原发性硬化性胆管炎（PSC）缺乏胆管上皮分子标志物。我们分析了最近全基因组关联研究（GWAS）中确定的疾病易感性基因的候选标志物。

方法

分析了 PSC 患者和对照者的存档肝组织中 GWAS 基因的表达水平。进行免疫组织化学分析以评估 PSC（N=45）和对照者（N=12）胆管上皮中的表达水平。将原发性胆汁性胆管炎（PBC）患者的样本用作疾病对照（N=20）。

结果

PSC 组的肝组织中 ATXN2、HHEX、PRDX5、MST1 和 TNFRSF14 的表达水平明显改变。我们重点关注免疫相关受体 TNFRSF14。免疫组织化学显示，仅在 PSC 组中观察到胆管上皮细胞中 TNFRSF14 的高表达。此外，编码 TNFRSF14 激活配体的 LIGHT 在 PSC 肝中的表达增加。免疫组织化学显示，PSC 胆管上皮中 LIGHT 的高表达（53%）比 PBC（15%）或对照（0%）组更为常见；此外，尽管它不是独立的预后因素，但它与纤维化进展呈正相关。