ArticleLangenbeck's archives of surgery2012
Deficiency of the oxygen sensor PHD1 augments liver regeneration after partial hepatectomy.
Article in Langenbeck's archives of surgery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration.Scientific reports · 2020Article
- Hypoxia signaling in human diseases and therapeutic targets.Experimental & molecular medicine · 2019Review
- Liver Zonation in Health and Disease: Hypoxia and Hypoxia-Inducible Transcription Factors as Concert Masters.International journal of molecular sciences · 2019Review
- Review
- The PHD1 oxygen sensor in health and disease.The Journal of physiology · 2018Review
- Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease.International journal of molecular sciences · 2018Review
- Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Oxygen, Metabolism, and Regeneration: Lessons from Mice.Trends in molecular medicine · 2017Review
- Hypoxia-inducible factors as molecular targets for liver diseases.Journal of molecular medicine (Berlin, Germany) · 2016Review
- PHD2: from hypoxia regulation to disease progression.Hypoxia (Auckland, N.Z.) · 2016Review
- PHD1 regulates p53-mediated colorectal cancer chemoresistance.EMBO molecular medicine · 2015Article
- Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges.Hypoxia (Auckland, N.Z.) · 2015Review
- Molecular mechanisms of action and therapeutic uses of pharmacological inhibitors of HIF-prolyl 4-hydroxylases for treatment of ischemic diseases.Antioxidants & redox signaling · 2014Review
- Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism.Hypoxia (Auckland, N.Z.) · 2014Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeLiver regeneration after partial hepatectomy (PH) occurs in conditions of reduced oxygen supply. HIF prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3) are oxygen sensors involved in adaptive response to hypoxia. Specific functions of these PHD enzymes in liver regeneration have, however, remained enigmatic. Here, we investigated the significance of PHD1 in liver regeneration following hepatectomy.
methodsLiver regeneration was studied in PHD1-deficient (PHD1(-/-)) and wild type (WT) mice subjected to 80% hepatectomy. For in vitro analyses, hepatocytes were isolated from PHD1(-/-) and WT livers. Cell cycle progression was studied via FACS-based analysis of nuclear DNA profile. Transcription factor binding assays, qRT-PCR, and immunoblotting were applied to study the relevance of PHD1 downstream effectors during liver regeneration.
resultsLiver regeneration was significantly enhanced in PHD1(-/-) mice compared to WT littermates. This effect was due to enhanced proliferation rather than to hypertrophy of liver cells. Cell cycle progression was significantly enhanced, and transcriptional activity of the cell cycle regulator c-Myc was increased in PHD1-deficient hepatocytes. These changes coincided with increased expression of cyclin D2, a cell cycle-promoting c-Myc target, and decreased expression of the cell cycle-delaying c-Myc target p21.
conclusionsLoss of PHD1 enhances liver regeneration by boosting hepatocyte proliferation in a c-Myc-dependent fashion. PHD1 might, therefore, represent a potential target to facilitate liver regeneration after surgical resection.
Indexed as
Identifiers
What OpenQuestion holds
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.