IGFBP4是原发性胆汁性胆管炎的指标，可减轻胆汁上皮细胞损伤
IGFBP4 is a Metric for Primary Biliary Cholangitis and Attenuates Biliary Epithelial Cell Injury.
摘要(中文译文)
免疫介导的胆管损伤是自身免疫性胆汁淤积性肝病的主要组织学特征。巨噬细胞是肝脏中最丰富的免疫细胞群，被认为在胆道修复中起着关键作用。然而，尚不清楚活化的巨噬细胞是否与受损的胆管上皮细胞相互作用。我们使用RNA测序、ELISA和免疫组织化学分析评估了来自PBC、PSC和健康对照的292个样本的原代单核细胞、MDMΦ、血清和肝组织切片中胰岛素样生长因子结合蛋白4（IGFBP4）的表达。通过磷酸激酶阵列检测IGFBP4在人肝内胆管上皮细胞中的作用所涉及的信号通路。在此，我们证明了胰岛素样生长因子结合蛋白4（IGFBP4）在巨噬细胞和胆管细胞相互作用中的作用。重要的是，PBC患者血清IGFBP4水平显著升高，与胆红素水平呈负相关。此外，免疫组织化学显示，在PBC肝脏中，IGFBP4阳性细胞不仅位于导管周围区域，还位于门静脉周围。体外研究表明，IGFBP4保护胆管细胞免受胆汁盐诱导的细胞损伤，促进胆管细胞增殖，这与胆汁酸受体TGR5、胆汁酸外排转运蛋白SLCO3A1的表达降低以及GSK-3β/β-catenin信号通路的激活有关。这些数据强调，IGFBP4不仅是PBC的潜在生物标志物，而且对胆管损伤起着保护作用。
Abstract
Immune-mediated bile duct injury is the primary histological feature of autoimmune cholestatic liver diseases. Macrophages, the most abundant immune cell population in the liver, have been postulated to play a critical role in biliary repair. However, it is unclear whether activated macrophages interact with injured biliary epithelial cells. We evaluated the expression of insulin-like growth factor-binding protein 4 (IGFBP4) in primary monocytes, MDMΦ, serum, and liver tissue sections from a total of 292 samples from PBC, PSC, and healthy controls using RNA-sequencing, ELISA, and immunohistochemistry analysis. The signal pathways involved in the effect of IGFBP4 in human intrahepatic biliary epithelial cells were examined by phospho-kinase arrays. Herein we demonstrate a role for insulin-like growth factor binding protein 4 (IGFBP4) in the interaction of macrophages and biliary cells. Importantly, the serum levels of IGFBP4 are significantly increased in PBC and negatively correlate with bilirubin levels. Furthermore, immunohistochemistry revealed an increase in IGFBP4 positive cells located not only in the periductal area but also around the portal tract in the PBC liver. In vitro study indicated that IGFBP4 protected biliary cells from bile salt-induced cell injury and promoted biliary cell proliferation, which was associated with reduced expression of the bile acid receptor TGR5, bile acid efflux transporter SLCO3A1, and activation of the GSK-3β/β-catenin signalling pathway. These data highlight that IGFBP4 not only serves as a potential biomarker for PBC but also plays a protective role against bile duct injury.
如何引用
AMA
Xing Zhou, Shuyu Shao, Danning Yang, Ziyan Cheng, Toshihiro Tanaka, Patrick S C Leung, et al. IGFBP4 is a Metric for Primary Biliary Cholangitis and Attenuates Biliary Epithelial Cell Injury.. Liver international : official journal of the International Association for the Study of the Liver. 2026; doi:10.1111/liv.70525.
APA
Xing Zhou, Shuyu Shao, Danning Yang, Ziyan Cheng, Toshihiro Tanaka, Patrick S C Leung, et al (2026). IGFBP4 is a Metric for Primary Biliary Cholangitis and Attenuates Biliary Epithelial Cell Injury.. Liver international : official journal of the International Association for the Study of the Liver. https://doi.org/10.1111/liv.70525
GB/T 7714
Xing Zhou, Shuyu Shao, Danning Yang, Ziyan Cheng, Toshihiro Tanaka, Patrick S C Leung, et al. IGFBP4 is a Metric for Primary Biliary Cholangitis and Attenuates Biliary Epithelial Cell Injury.[J]. Liver international : official journal of the International Association for the Study of the Liver, 2026 doi:10.1111/liv.70525.
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