Clonorchis sinensis infection is one of the risk factors that provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis and even cholangiocarcinoma (CCA). Disrupted or aberrant intercellular communication among liver-constituting cells leads to pathological states that cause various hepatic diseases. This study was designed to investigate the pathological changes caused by C. sinensis excretory-secretory products (ESPs) in non-cancerous human cell lines (cholangiocytes [H69 cell line] and human hepatic stellate cells [LX2 cell line]) and their intercellular crosstalk, as well the pathological changes in infected mouse liver tissues. The cells were treated with ESPs, following which transforming growth factor beta 1 (TGF-β1) and interleukin-6 (IL-6) secretion levels and epithelial-mesenchymal transition (EMT)- and fibrosis-related protein expression were measured. The ESP-mediated cellular motility (migration/invasion) between two cells was assessed using the Transwell and three-dimensional microfluidic assay models. The livers of C. sinensis-infected mice were stained using EMT and fibrotic marker proteins. Treatment of cells with ESPs increased TGF-β1 and IL-6 secretion and the expression of EMT- and fibrosis-related proteins. The ESP-mediated mutual cell interaction further affected the cytokine secretion and protein expression levels and promoted cellular motility. N-cadherin overexpression and collagen fiber deposition were observed in the livers of C. sinensis-infected mice. These findings suggest that EMT and biliary fibrosis occur through intercellular communication between cholangiocytes and hepatic stellate cells during C. sinensis infection, promoting malignant transformation and advanced hepatobiliary abnormalities.

中文翻译：

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华支睾吸虫感染期间胆管细胞与肝星状细胞之间的串扰促进上皮间质转化和导管周围纤维化的进展

华支睾吸虫感染是引发慢性炎症、上皮增生、导管周围纤维化甚至胆管癌（CCA）的危险因素之一。肝脏构成细胞之间的细胞间通讯中断或异常会导致导致各种肝脏疾病的病理状态。本研究旨在探讨中华线虫排泄物（ESP）对人非癌性细胞系（胆管细胞[H69细胞系]和人肝星状细胞[LX2细胞系]）引起的病理变化及其细胞间串扰。 ，以及感染小鼠肝组织的病理变化。用 ESP 处理细胞，然后测量转化生长因子 β 1 (TGF-β1) 和白细胞介素 6 (IL-6) 的分泌水平以及上皮间质转化 (EMT) 和纤维化相关蛋白的表达。使用 Transwell 和三维微流体测定模型评估 ESP 介导的两个细胞之间的细胞运动（迁移/入侵）。使用 EMT 和纤维化标记蛋白对中华支线虫感染小鼠的肝脏进行染色。用 ESP 处理细胞可增加 TGF-β1 和 IL-6 的分泌以及 EMT 和纤维化相关蛋白的表达。 ESP介导的细胞间相互作用进一步影响细胞因子分泌和蛋白质表达水平并促进细胞运动。在中华支线虫感染小鼠的肝脏中观察到N-钙粘蛋白过度表达和胶原纤维沉积。这些发现表明，中华线虫感染期间，通过胆管细胞和肝星状细胞之间的细胞间通讯发生EMT和胆道纤维化，促进恶性转化和晚期肝胆异常。