Peroxisome proliferator-activated receptor-β signaling contributes to enhanced proliferation of hepatic stellate cells
Open accessAbstract
Background & aims The peroxisome proliferator-activated nuclear receptors (PPAR-alpha, PPAR-beta, and PPAR-gamma), which modulate the expression of genes involved in energy homeostasis, cell cycle, and immune function, may play a role in hepatic stellate cell activation. Previous studies focused on the decreased expression of PPAR-gamma in hepatic stellate cell activation but did not investigate the expression and role of the PPAR-alpha and -beta isotypes. The aim of this study was to evaluate the expression of the different PPARs during hepatic stellate cell activation in vitro and in situ and to analyze possible factors that might contribute to their expression. In a second part of the study, the effect of a PPAR-beta agonist on acute liver injury was evaluated.Methods The effects of PPAR isotype-specific ligands on hepatic stellate cell transition were evaluated by bromodeoxyuridine incorporation, gel shifts, immunoprecipitation, and use of antisense PPAR-beta RNA-expressing adenoviruses. Tumor necrosis factor alpha-induced PPAR-beta phosphorylation and expression was evaluated by metabolic labeling and by using specific P38 inhibitors.Results Hepatic stellate cells constitutively express high levels of PPAR-beta, which become further induced during culture activation and in vivo fibrogenesis. No significant expression of PPAR-alpha or -gamma was found. Stimulation of the P38 mitogen-activated protein kinase pathway modulated the expression of PPAR-beta. Transcriptional activation of PPAR-beta by L165041 enhanced hepatic stellate cell proliferation. Treatment of rats with a single bolus of CCl(4) in combination with L165041 further enhanced the expression of fibrotic markers.Conclusions PPAR-beta is an important signal-transducing factor contributing to hepatic stellate cell proliferation during acute and chronic liver inflammation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PPAR-δ agonists such as L165041 increase hepatic stellate cell proliferation during inflammation in rats.
“PPAR-δ agonists, such as L165041, increased hepatic stellate cell proliferation during inflammation in rats [148]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [148]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 77 · Cited by 137
Research works printed but not linked: 6
- Miyahara T, Schrum L, Rippe R, Xiong S, Yee HF Jr, Motomura K, Anania FA, Willson TM, Tsukamoto H. PPAR and hepatic stellate cell activation. J Biol Chem 2000;275:35715-35722.
- Meade EA, McIntyre TM, Zimmerman GA, Prescott SM. Peroxi- some proliferators enhance cyclooxygenase-2 expression in epi- thelial cells. J Biol Chem 1999;274:8328 -8334.
- Granneman J, Skoff R, Yang X. Member of the peroxisome pro- liferator-activated receptor family of transcription factors is differ- entially expressed by oligodendrocytes. J Neurosci Res 1998;51: 563-573.
- Saluja I, Granneman JG, Skoff RP. PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 2001;33: 191-204.
- Hsi LC, Wilson L, Nixon J, Eling TE. 15-Lipoxygenase-1 metabo- lites down-regulate PPAR gamma via the MAP kinase signaling pathway. J Biol Chem 2001;276:34545-34552.
- Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W. The PPARalpha-leukotriene B4 pathway to inflammation con- trol. Nature 1996;384:39 -43.
- Authors
- Hellemans, K., Michalik, L., Dittie, A., Knorr, A., Rombouts, K., de Jong, J., Heirman, C., Quartier, E., Schuit, F., Wahli, W., & Geerts, A.
- Affiliations
- Université Libre de Bruxelles (BE)
- University of Lausanne (CH)
- Bayer (Germany) (DE)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 124
- Issue
- 1
- Pages
- 184-201
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2090954353
- Cited by
- 137
- References
- 77
- Citations by year
- 2025: 6 · 2024: 9 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 9 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 5 · 2012: 6
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- National Science Foundation
- Bayer
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fonds Wetenschappelijk Onderzoek
- Vrije Universiteit Brussel
- Universiteit Antwerpen
- Vlaamse regering
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- PPAR-beta, hepatic stellate cells, stellate cell activation, liver fibrosis, PPARα, PPARγ, p38 MAPK signaling, PPAR agonists, carbon tetrachloride, liver injury, TNF-α, cell proliferation, liver inflammation
- MeSH terms
- Fatty Acid-Binding Protein 7, Acute Disease, Adenoviridae, Animals, Carbon Tetrachloride, Carrier Proteins, Cell Differentiation, Cell Division, DNA, Extracellular Matrix, Genetic Vectors, Isoenzymes, Liver, Liver Cirrhosis, Liver Cirrhosis, Alcoholic, Liver Diseases, Male, Neoplasm Proteins, Nerve Tissue Proteins, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Transcription Factors, Signal Transduction, Antisense Elements (Genetics), Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Protein Isoforms, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Fatty Acid-Binding Proteins, Rats, Cyclooxygenase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
