ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2.Cell death & disease · 2026Article
- Purinergic Receptor P2Y2 Activity Prevents DNA Damage in CClJournal of cellular biochemistry · 2025Article
- Purinergic signaling in liver disease: calcium signaling and induction of inflammation.Purinergic signalling · 2025Review
- The P2YPurinergic signalling · 2024Article
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- P2Y2 purinergic receptor gene deletion protects mice from bacterial endotoxin and sepsis-associated liver injury and mortality.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Therapeutic potential for P2YPurinergic signalling · 2023Review
- The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates.Cell death & disease · 2022Review
- Liver Trauma: Until When We Have to Delay Surgery? A Review.Life (Basel, Switzerland) · 2022Review
- Blockade of the P2Y2 Receptor Attenuates Alcoholic Liver Inflammation by Targeting the EGFR-ERK1/2 Signaling Pathway.Drug design, development and therapy · 2022Article
- Receptor-specific CaiScience · 2021Article
- Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension.International journal of environmental research and public health · 2021Review
- P2Y2R Deficiency Ameliorates Hepatic Steatosis by Reducing Lipogenesis and Enhancing Fatty Acid β-Oxidation through AMPK and PGC-1α Induction in High-Fat Diet-Fed Mice.International journal of molecular sciences · 2021Article
- Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities.JHEP reports : innovation in hepatology · 2020Review
- Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes-Potential Applications for Diabetes and NAFLD.Biomolecules · 2020Review
- Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection.Hepatology communications · 2020Article
- Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CClInternational journal of molecular sciences · 2020Article
- P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction.Frontiers in pharmacology · 2020Review
- Purinergic signaling in hepatic disease.Purinergic signalling · 2019Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Extracellular nucleotides via activation of P2 purinergic receptors influence hepatocyte proliferation and liver regeneration in response to 70% partial hepatectomy (PH). Adult hepatocytes express multiple P2Y (G protein-coupled) and P2X (ligand-gated ion channels) purinergic receptor subtypes. However, the identity of key receptor subtype(s) important for efficient hepatocyte proliferation in regenerating livers remains unknown. To evaluate the impact of P2Y2 purinergic receptor-mediated signaling on hepatocyte proliferation in regenerating livers, wild-type (WT) and P2Y2 purinergic receptor knockout (P2Y2-/-) mice were subjected to 70% PH. Liver tissues were analyzed for activation of early events critical for hepatocyte priming and subsequent cell cycle progression. Our findings suggest that early activation of p42/44 ERK MAPK (5 min), early growth response-1 (Egr-1) and activator protein-1 (AP-1) DNA-binding activity (30 min), and subsequent hepatocyte proliferation (24-72 h) in response to 70% PH were impaired in P2Y2-/- mice. Interestingly, early induction of cytokines (TNF-α, IL-6) and cytokine-mediated signaling (NF-κB, STAT-3) were intact in P2Y2-/- remnant livers, uncovering the importance of cytokine-independent and nucleotide-dependent early priming events critical for subsequent hepatocyte proliferation in regenerating livers. Hepatocytes isolated from the WT and P2Y2-/- mice were treated with ATP or ATPγS for 5-120 min and 12-24 h. Extracellular ATP alone, via activation of P2Y2 purinergic receptors, was sufficient to induce ERK phosphorylation, Egr-1 protein expression, and key cyclins and cell cycle progression of hepatocytes in vitro. Collectively, these findings highlight the functional significance of P2Y2 purinergic receptor activation for efficient hepatocyte priming and proliferation in response to PH.
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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.