The crosstalk between cholangiocytes and hepatic stellate cells promotes the progression of epithelial-mesenchymal transition and periductal fibrosis during Clonorchis sinensis infection.

Publisher: BioMed Central Country of Publication: England NLM ID: 101462774 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-3305 (Electronic) Linking ISSN: 17563305 NLM ISO Abbreviation: Parasit Vectors Subsets: MEDLINE

Original Publication: London : BioMed Central

Clonorchiasis*/metabolism ; Clonorchis sinensis*/metabolism ; Bile Duct Neoplasms*/metabolism ; Bile Duct Neoplasms*/pathology; Humans ; Animals ; Mice ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Hepatic Stellate Cells/metabolism ; Fibrosis ; Bile Ducts, Intrahepatic ; Epithelial-Mesenchymal Transition

ABSTRACT: BACKGROUND: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
(© 2024. The Author(s).)

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2020R1F1A1071492 National Research Foundation of Korea

Keywords: Clonorchis sinensis; Cholangiocytes; Epithelial-mesenchymal transition; Excretory-secretory products; Hepatic stellate cells; Intercellular crosstalk; Periductal fibrosis

0 (Transforming Growth Factor beta1)
0 (Interleukin-6)

Date Created: 20240323 Date Completed: 20240325 Latest Revision: 20240325

20250114

PMC10958959

10.1186/s13071-024-06236-2

38519993