ArticleProceedings of the National Academy of Sciences of the United States of America2017
Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Pooled it
- Subcutaneous efgartigimod PH20 in generalized myasthenia gravis: A phase 3 randomized noninferiority study (ADAPT-SC) and interim analyses of a long-term open-label extension study (ADAPT-SC+).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Trial
- Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.Science advances · 2019Trial
- Targeting FcRn for immunomodulation: a promising therapy in autoimmune inflammatory rheumatic diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Targeted cellular depletion in an immune-liver-on-a-chip platform elucidates cell-type-specific heterogeneity in drug-induced hepatotoxicity.Communications biology · 2025Article
- Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK.Molecular metabolism · 2025Article
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- A model predicting the 6-year all cause mortality of patients with advanced schistosomiasis after discharge: Derived from a large population-based cohort study.PLoS neglected tropical diseases · 2025Article
- FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology.Cell metabolism · 2025Article
- The FcRn from gene to protein and function: comparison between species.Frontiers in immunology · 2025Review
- Engineered serum markers for non-invasive monitoring of gene expression in the brain.Nature biotechnology · 2024Article
- Differential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin.JCI insight · 2024Article
- Mono-amino acid linkers enable highly potent small molecule-drug conjugates by conditional release.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Albumin, an interesting and functionally diverse protein, varies from 'native' to 'effective' (Review).Molecular medicine reports · 2024Review
- FcRn Expression in Endometrial Cancer and Its Association with Clinicopathologic Features.Diagnostics (Basel, Switzerland) · 2023Article
- Hypoosmosis alters hepatocyte mitochondrial morphology and induces selective release of carbamoyl phosphate synthetase 1.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- FcRn inhibitors: a novel option for the treatment of myasthenia gravis.Neural regeneration research · 2023Review
- Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- The therapeutic age of the neonatal Fc receptor.Nature reviews. Immunology · 2023Review
- Biopsy-based single-cell transcriptomics reveals MAIT cells as potential targets for controlling fibrosis-related liver inflammation due to chronic hepatitis-B infection.Clinical and translational medicine · 2022Article
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
Abstract
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn-albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity.
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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.