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Objective: To investigate whether lipopolysaccharide (LPS) stimulates cholangiocyte proliferation via the IL-6/STAT3 pathway in vivo.
Methods: Rats were randomized into three groups: LPS group (injected intravenously with LPS 2.5 mg/kg), anti-IL-6 group (injected intravenously with anti-IL-6 0.5 mg/kg 1hr after LPS injection), and control group. At 6, 12, 24, 48 and 72 h after LPS injection, LPS concentration in plasma was detected by kinetic turbidimetric limulus test. IL-6 concentrations in liver homogenate was determinded by ELISA, cholangiocyte proliferation was checked by immunohistochemistry, expression of IL-6 mRNA was quantified by real-time RT-PCR, the level of phophorylated-STAT3 (P-STAT3) protein was analyzed by western blotting.
Results: Cholangiocytes responded to LPS by a marked increase in cell proliferation, IL-6 secretion and P-STAT3 expression. Anti-IL-6 neutralizing antibody inhibited LPS-induced cholangiocytes proliferation, and decreased levels of IL-6 and p-STAT3.
Conclusions: LPS promotes cholangiocyte proliferation through the IL-6/STAT3 pathway.
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Cell Mol Gastroenterol Hepatol
September 2025
Ajmera Transplant Centre, University Health Network, Toronto, ON; Department of Immunology, University of Toronto, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON. Electronic address:
Background & Aims: Interleukin-4 (IL-4) is a key contributor to liver regeneration but its effects remain poorly understood due to a lack of models that preserve the complex cellular interactions of the liver. Here, we use murine precision-cut liver slices (PCLS), a 3D tissue culture system that maintains both parenchymal and non-parenchymal cells, to investigate the role of IL-4 in hepatic cell reprogramming. Through longitudinal single-cell transcriptomics and protein-level validation, we demonstrate the pro-regenerative potential of IL-4.
View Article and Find Full Text PDFHum Cell
August 2025
The Second Clinical Medical College, Lanzhou University, Lanzhou, 730000, China.
Cholangiocarcinoma (CCA) is a highly heterogeneous primary malignant tumor of the biliary tract. Intrahepatic and extrahepatic cholangiocytes originate from different sources, resulting in significant clinical, epidemiological, molecular, and genetic heterogeneity. Globally, the incidence and mortality rates of CCA are generally increasing, highlighting the need for more foundational research to support advances in clinical diagnosis and treatment.
View Article and Find Full Text PDFPharmacol Ther
August 2025
Laboratory of Cell Growth and Differentiation, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address:
The liver comprises hepatic parenchymal cells, primarily hepatocytes, and non-parenchymal cells such as liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), and cholangiocytes. These cell types interact with each other to maintain homeostasis through metabolism, detoxification, and protein synthesis. Such cellular interactions also play crucial roles in regulating the onset and progression of liver diseases.
View Article and Find Full Text PDFJ Pediatr Surg
August 2025
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Shanghai, China. Electronic address:
Purpose: N6-methyladenosine (m6A) is involved in biliary atresia (BA), however the underlying mechanisms remain unknown. This study aims to explore the involvement of m6A modification and its role in epithelial-to-mesenchymal transition (EMT) in BA cholangiocytes.
Method: A published single-cell RNA sequencing dataset (HRA003163) was analyzed, focusing on cholangiocytes for differential gene expression, pathway enrichment, and correlation analyses.
Front Cell Dev Biol
July 2025
NHC Key Laboratory of Radiobiology, College of Public Health, Jilin University, Changchun, China.
Liver fibrosis is induced by persistent stimulation of various factors, resulting from complex multicellular interactions and multifactorial networks. Without intervention, it can progress to cirrhosis and even liver cancer. Current understanding suggests that liver fibrosis is reversible, making it crucial to explore effective therapeutic strategies for its alleviation.
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