ArticleFrontiers in pharmacology2014
Activation of adenosine receptor A2A increases HSC proliferation and inhibits death and senescence by down-regulation of p53 and Rb.
Article in Frontiers in pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters.Nature communications · 2025Article
- Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury.Frontiers in transplantation · 2025Review
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- Coffee, adenosine, and the liver.Purinergic signalling · 2024Review
- The different effects of four adenosine receptors in liver fibrosis.Frontiers in pharmacology · 2024Article
- Adenosine A2A receptor activation reduces chondrocyte senescence.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase/protein kinase B signaling pathway in mice.Journal of exercise rehabilitation · 2022Article
- [Advances in the study of the role of adenosine 2A receptor in liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Review
- Purinergic Signaling in Liver Pathophysiology.Frontiers in endocrinology · 2021Review
- Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities.JHEP reports : innovation in hepatology · 2020Review
- Polydeoxyribonucleotide Exerts Protective Effect Against CClInternational journal of molecular sciences · 2020Article
- cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease.Biomolecules · 2020Review
- Article
- Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- Role of Cardiac AFrontiers in pharmacology · 2020Review
- Interleukin‑10 promotes primary rat hepatic stellate cell senescence by upregulating the expression levels of p53 and p21.Molecular medicine reports · 2018Article
- Pharmacologically induced reversible hypometabolic state mitigates radiation induced lethality in mice.Scientific reports · 2017Article
- Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings.Clinical and experimental medicine · 2017Review
- Signaling pathways involving adenosine A2A and A2B receptors in wound healing and fibrosis.Purinergic signalling · 2016Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimsDuring fibrosis hepatic stellate cells (HSC) undergo activation, proliferation, and senescence but the regulation of these important processes is poorly understood. The adenosine A2A receptor (A2A) is known to be present on HSC, and its activation results in liver fibrosis. In this study, we tested if A2A has a role in the regulation of HSC proliferation, apoptosis, senescence, and the relevant molecular mechanism.
methodsThe ability of adenosine to regulate p53 and Rb protein levels, proliferation, apoptosis and senescence was tested in the human HSC cell line LX-2 and rat primary HSC.
resultsAdenosine receptor activation down-regulates p53 and Rb protein levels, increases BrdU incorporation and increases cell survival in LX-2 cells and in primary rat HSC. These effects of NECA were reproduced by an adenosine A2A receptor specific agonist (CGS21680) and blocked by a specific antagonist (ZM241385). By day twenty-one of culture primary rat HSC entered senescence and expressed β-gal which was significantly inhibited by NECA. Furthermore, NECA induced down regulation of p53 and Rb and Rac1, and decreased phosphorylation of p44-42 MAP Kinase in LX-2 cells and primary rat HSC. These effects were reproduced by the cAMP analog 8-Bromo-cAMP, and the adenylyl cyclase activator forskolin, and were blocked by PKA inhibitors.
conclusionsThese results demonstrate that A2A receptor regulates a number of HSC fate decisions and induces greater HSC proliferation, reduces apoptosis and senescence by decreasing p53 and Rb through cAMP-PKA/Rac1/p38 MAPK pathway. This provides a mechanism for adenosine induced HSC regulation and liver fibrosis.
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