ArticleThe Journal of biological chemistry2011
Cholangiocyte N-Ras protein mediates lipopolysaccharide-induced interleukin 6 secretion and proliferation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Clinical guidelines for primary sclerosing cholangitis 2017.Journal of gastroenterology · 2018Guideline
- Multicohort Validation of Gut Microbiome Signatures for Cholangiocarcinoma Diagnosis and Functional Characterization of Bifidobacterium Pseudocatenulatum.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Taurocholic acid induces intrahepatic cholangiocyte cell proliferation via activating NRAS and YAP1.PloS one · 2026Article
- Central role for cholangiocyte pathobiology in cholestatic liver diseases.Hepatology (Baltimore, Md.) · 2025Review
- Review
- Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling.Hepatology (Baltimore, Md.) · 2025Article
- Article
- The Functional Roles of Immune Cells in Primary Liver Cancer.The American journal of pathology · 2022Review
- Role of Immune Cells in Biliary Repair.Frontiers in immunology · 2022Review
- Down-regulation of STAT3 enhanced chemokine expression and neutrophil recruitment in biliary atresia.Clinical science (London, England : 1979) · 2021Article
- Senescent cholangiocytes release extracellular vesicles that alter target cell phenotype via the epidermal growth factor receptor.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
- Article
- The transcription factor ETS1 promotes apoptosis resistance of senescent cholangiocytes by epigenetically up-regulating the apoptosis suppressor BCL2L1.The Journal of biological chemistry · 2019Article
- Druggable Targets in Cyclic Nucleotide Signaling Pathways in Apicomplexan Parasites and Kinetoplastids against Disabling Protozoan Diseases in Humans.International journal of molecular sciences · 2019Review
- Aging-Related Molecular Pathways in Chronic Cholestatic Conditions.Frontiers in medicine · 2019Review
- Metabolomic Profiling of Portal Blood and Bile Reveals Metabolic Signatures of Primary Sclerosing Cholangitis.International journal of molecular sciences · 2018Article
- Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies.International journal of molecular sciences · 2018Review
- Knockout of microRNA-21 attenuates alcoholic hepatitis through the VHL/NF-κB signaling pathway in hepatic stellate cells.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Macrophages contribute to the pathogenesis of sclerosing cholangitis in mice.Journal of hepatology · 2018Article
- Mechanisms of cholangiocyte responses to injury.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cholangiocytes, the epithelial cells lining the bile ducts in the liver, are periodically exposed to potentially injurious microbes and/or microbial products. As a result, cholangiocytes actively participate in microbe-associated, hepatic proinflammatory responses. We previously showed that infection of cultured human cholangiocytes with the protozoan parasite, Cryptosporidium parvum, or treatment with gram-negative bacteria-derived LPS, activates NFκB in a myeloid differentiation 88 (MyD88)-dependent manner. Here, we describe a novel signaling pathway initiated by Toll-like receptors (TLRs) involving the small GTPase, Ras, that mediates cholangiocyte proinflammatory cytokine production and induction of cholangiocyte proliferation. Using cultured human cholangiocytes and a Ras activation assay, we found that agonists of plasma membrane TLRs (TLR 1, 2, 4, 5, and 6) rapidly (<10 min) activated N-Ras, but not other p21 Ras isoforms, resulting in the rapid (<15 min) phosphorylation of the downstream Ras effector, ERK1/2. RNA interference-induced depletion of TRAF6, a downstream effector of MyD88 and known activator of MAPK signaling, had no effect on N-Ras activation. Following N-Ras activation the proinflammatory cytokine, IL6, is rapidly secreted. Using a luciferase reporter, we demonstrated that LPS treatment induced IL6 promoter-driven luciferase which was suppressed using MEK/ERK pharmacologic inhibitors (PD98059 or U0126) and RNAi-induced depletion of N-Ras. Finally, we showed that LPS increased cholangiocyte proliferation (1.5-fold), which was inhibited by depletion of N-Ras; TLR agonist-induced proliferation was also inhibited following pretreatment with an IL6 receptor-blocking antibody. Together, our results support a novel signaling axis involving microbial activation of N-Ras likely involved in the cholangiocyte pathogen-induced proinflammatory response.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.