ArticleJournal of hepatology2012
A hedgehog survival pathway in 'undead' lipotoxic hepatocytes.
Article in Journal of hepatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity.Hepatology (Baltimore, Md.) · 2015Trial
- An LSEC-focused computational drug repurposing platform for liver fibrosis: Identification of vorinostat and other LSEC-protective candidates.bioRxiv : the preprint server for biology · 2026Article
- Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming.Journal of clinical and translational hepatology · 2024Article
- Lipid Droplet-Associated Proteins Perilipin 1 and 2: Molecular Markers of Steatosis and Microvesicular Steatotic Foci in Chronic Hepatitis C.International journal of molecular sciences · 2022Article
- Osteogenic growth peptide enhances osteogenic differentiation of human periodontal ligament stem cells.Heliyon · 2022Article
- In vitro ballooned hepatocytes can be produced by primary human hepatocytes and hepatic stellate cell sheets.Scientific reports · 2022Article
- High frequency and long persistency of ballooning hepatocyte were associated with glucose intolerance in patients with severe obesity.Scientific reports · 2021Article
- Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): a promising new therapy.Cellular & molecular biology letters · 2021Review
- Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer.International journal of molecular sciences · 2021Review
- How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?Hepatology international · 2021Review
- Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis.Cells · 2020Review
- Nonalcoholic fatty liver disease and type 2 diabetes: where do Diabetologists stand?Clinical diabetes and endocrinology · 2020Review
- Noninvasive diagnostic criteria for nonalcoholic steatohepatitis based on gene expression levels in peripheral blood mononuclear cells.Journal of gastroenterology · 2019Article
- Response to the letter by Sumida et al. regarding our manuscript "Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease".Journal of gastroenterology · 2019Article
- Molecular pathways of nonalcoholic fatty liver disease development and progression.Cellular and molecular life sciences : CMLS · 2019Review
- Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease.Journal of gastroenterology · 2018Observational
- To die or not to die: death signaling in nonalcoholic fatty liver disease.Journal of gastroenterology · 2018Review
- Apoptosis and non-alcoholic fatty liver diseases.World journal of gastroenterology · 2018Review
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsBallooned hepatocytes in non-alcoholic steatohepatitis (NASH) generate sonic hedgehog (SHH). This observation is consistent with a cellular phenotype in which the cell death program has been initiated but cannot be executed. Our aim was to determine whether ballooned hepatocytes have potentially disabled the cell death execution machinery, and if so, can their functional biology be modeled in vitro.
methodsImmunohistochemistry was performed on human NASH specimens. In vitro studies were performed using HuH-7 cells with shRNA targeted knockdown of caspase 9 (shC9 cells) or primary hepatocytes from caspase 3(-/-) mice.
resultsBallooned hepatocytes in NASH display diminished expression of caspase 9. This phenotype was modeled using shC9 cells; these cells were resistant to lipoapoptosis by palmitate (PA) or lysophosphatidylcholine (LPC) despite lipid droplet formation. During lipid loading by either PA or LPC, shC9 cells activate JNK which induces SHH expression via AP-1. An autocrine hedgehog survival signaling pathway was further delineated in both shC9 and caspase 3(-/-) cells during lipotoxic stress.
conclusionsBallooned hepatocytes in NASH downregulate caspase 9, a pivotal caspase executing the mitochondrial pathway of apoptosis. Hepatocytes engineered to reduce caspase 9 expression are resistant to lipoapoptosis, in part, due to a hedgehog autocrine survival signaling pathway.
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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.