ArticleMolecular biology of the cell2015
CHOP links endoplasmic reticulum stress to NF-κB activation in the pathogenesis of nonalcoholic steatohepatitis.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 115 citations in OpenAlex.
- Article
- Zinc accumulation in macrophages exacerbates metabolic dysfunction-associated steatotic liver disease progression.Signal transduction and targeted therapy · 2026Article
- Dietary cauliflower (Brassica oleracea var. botrytis) mitigates benzo[a]pyrene-induced oxidative stress, immune dysfunction, and tissue damage in Nile tilapia.Scientific reports · 2026Article
- Mitochondrial dysfunction in type 1 diabetes and its implications for pancreatic beta-cell survival and insulin secretion.Acta diabetologica · 2026Review
- HIF-2α induction in de novo lipogenesis in metabolic dysfunction-associated steatohepatitis is dependent on IL-21 signaling.The Journal of biological chemistry · 2026Article
- Article
- OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies.Communications biology · 2025Article
- Hepato-Renal Crosstalk in Acute and Chronic Disease: From Shared Pathways to Therapeutic Targets.Biomedicines · 2025Review
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Altered mitochondrial unfolded protein response and FGF21 secretion in MASLD progression and the effect of exercise intervention.Scientific reports · 2025Article
- The PI3K/Akt/mTOR Pathway: Immuno-Metabolic Orchestration in IR/MASH-Associated Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- TNIK-driven regulation of ERK5 transcriptional activity in endothelial cells.Frontiers in cardiovascular medicine · 2025Article
- 6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress.Molecules (Basel, Switzerland) · 2024Article
- Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy.EMBO molecular medicine · 2024Article
- A beneficial adaptive role for CHOP in driving cell fate selection during ER stress.EMBO reports · 2024Article
- Implications of endoplasmic reticulum stress and autophagy in aging and cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Ac-SDKP attenuates ER stress-stimulated collagen production in cardiac fibroblasts by inhibiting CHOP-mediated NF-κB expression.Frontiers in pharmacology · 2024Article
- Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A beneficial adaptive role for CHOP in driving cell fate selection during ER stress.bioRxiv : the preprint server for biology · 2023Article
- Rhamnetin ameliorates non-alcoholic steatosis and hepatocellular carcinoma in vitro.Molecular and cellular biochemistry · 2023Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Free fatty acid induction of inflammation and cell death is an important feature of nonalcoholic steatohepatitis (NASH) and has been associated with disruption of the endoplasmic reticulum and activation of the unfolded protein response (UPR). After chronic UPR activation, the transcription factor CHOP (GADD153/DDIT3) triggers cell death; however, the mechanisms linking the UPR or CHOP to hepatoceullular injury and inflammation in the pathogenesis of NASH are not well understood. Using HepG2 and primary human hepatocytes, we found that CHOP induces cell death and inflammatory responses after saturated free fatty acid exposure by activating NF-κB through a pathway involving IRAK2 expression, resulting in secretion of cytokines IL-8 and TNFα directly from hepatocytes. TNFα facilitates hepatocyte death upon exposure to saturated free fatty acids, and secretion of both IL-8 and TNFα contribute to inflammation. Of interest, CHOP/NF-κB signaling is not conserved in primary rodent hepatocytes. Our studies suggest that CHOP plays a vital role in the pathophysiology of NASH by induction of secreted factors that trigger inflammation and hepatocellular death via a signaling pathway specific to human hepatocytes.
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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.