ArticleJournal of molecular medicine (Berlin, Germany)2013
ERK controls epithelial cell death receptor signalling and cellular FLICE-like inhibitory protein (c-FLIP) in ulcerative colitis.
Article in Journal of molecular medicine (Berlin, Germany), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Integrated Single Cell Spatial Analysis Reveals Dysregulated Basal Progenitor Cells in Ulcerative Colitis Pathogenesis: A Multi Omics Study.Health science reports · 2026Article
- Biological Functions and Clinical Implications of CFLAR: From Cell Death Mechanisms to Therapeutic Targeting in Immune Regulation.Journal of inflammation research · 2025Review
- TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis.Acta pharmacologica Sinica · 2023Article
- Article
- The many faces of tumor necrosis factor signaling in the intestinal epithelium.Genes and immunity · 2019Review
- c-FLIP, a Novel Biomarker for Cancer Prognosis, Immunosuppression, Alzheimer's Disease, Chronic Obstructive Pulmonary Disease (COPD), and a Rationale Therapeutic Target.Biomarkers journal · 2019Article
- hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes.Bioscience reports · 2018Article
- Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Non-Hematopoietic β-Arrestin1 Confers Protection Against Experimental Colitis.Journal of cellular physiology · 2016Article
- Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL).Marine drugs · 2015Review
- Differential Regulation of NOTCH2 and NOTCH3 Contribute to Their Unique Functions in Vascular Smooth Muscle Cells.The Journal of biological chemistry · 2015Article
- Identification of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2.DNA research : an international journal for rapid publication of reports on genes and genomes · 2014Article
- Ethanol Extract of Antrodia camphorata Grown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Tacrolimus Up-regulates Expression of TGFβ Receptor Type IIIn vivo (Athens, Greece)Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal epithelial cell (IEC) death signalling through the Fas receptor is impaired in active ulcerative colitis (UC). This is possibly due to the activation of cytoprotective pathways resulting in limitation of the tissue injury secondary to inflammation. We hypothesized that inflammatory signalling like the nuclear factor (NF)-κB or mitogen activated protein kinase (MAPK) pathways could be involved in (a) the modification of Fas mediated apoptosis responses and (b) the regulation of the Fas receptor inhibitor cellular FLICE-like inhibitory protein (c-FLIP). Phospho-ERK was upregulated in IECs in active UC as well as IECs exposed to pro-inflammatory cytokines in vitro. Similarly, the short form of c-FLIP (c-FLIPS) was found to be upregulated in IECs from patients with active UC. c-FLIPS was the main splice variant found in both HT-29 cells and primary human IECs. Both splice variants were induced by TNF-α, IL-1β and IFN-γ, while IL-10 induced c-FLIPL expression; TNF-α also induced c-FLIPS in primary IECs. Inhibition of NF-κB, JNK and p38 pathways did not affect c-FLIP expression, whereas ERK inhibition by MEK1 RNA silencing and pharmacologic inhibitors decreased c-FLIPS expression. Similarly, ERK - but not NF-κB - inhibited Fas ligand and TNF-α-mediated apoptosis responses in both cell line experiments and primary IECs. The present study identifies the MEK-ERK pathway as a major regulator of apoptosis in IECs during flares of UC and an inducer of c-FLIPS. The results explain the resistance to receptor mediated epithelial apoptosis in active UC. Oncogenic c-FLIP could promote propagation of DNA-damaged IECs and contribute to cancer development in UC.
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