ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2019
LGR4 protects hepatocytes from injury in mouse.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 26 citations in OpenAlex.
- Endothelial cell LGR4 maintains liver sinusoidal endothelial cell Identity and protects against hepatic steatosis.Life sciences · 2026Article
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- Intestinal LGR4 Signalling Alters Bacterial translocation, Intrahepatic Microbiota composition, and Type 1 Interferon Expression in Murine Liver Fibrosis.Inflammation · 2025Article
- Deficiency of Leucine-Rich Repeat Containing G Protein-Coupled Receptor 4 in Pancreas Reduces β Cell Mass.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK.Molecular metabolism · 2025Article
- The Genomic Landscape of Wilson Disease in a Pan India Disease Cohort and Population-Scale Data.Movement disorders clinical practice · 2025Article
- Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/β-catenin signaling pathway.Gastroenterologia y hepatologia · 2024Article
- Case report: exome sequencing identified mutations in theFrontiers in endocrinology · 2024Article
- Regulation of hepatic lipid metabolism by intestine epithelium-derived exosomes.Life metabolism · 2023Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- The role of roof plate-specific spondins in liver homeostasis and disease.Liver research (Beijing, China) · 2022Review
- Bioinformatics Analysis ofBiomolecules · 2022Article
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- Role of R-spondin 2 in arterial lymphangiogenesis and atherosclerosis.Cardiovascular research · 2021Article
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- LGR4 silence aggravates ischemic injury by modulating mitochondrial function and oxidative stress via ERK signaling pathway in H9c2 cells.Journal of molecular histology · 2021Article
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα-SREBP2 pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Association of WNT7B and RSPO1 with Axial Length in School Children.Investigative ophthalmology & visual science · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Leucine-rich repeat G protein-coupled receptors (LGRs) and their endogenous ligands R-spondin1-4 (Rspo) are critical in embryonic development and in maintenance of stem cells. The functions of the Rspo-LGR system in differentiated cells remain uncharacterized. In this study, the expression profiles of LGRs and Rspos were characterized in mature hepatocytes. A liver-specific knockout of LGR4 in mouse was generated and used to study hepatic ischemia/reperfusion-induced injury (HIRI) as well as lipopolysaccharide/ D- galactosamine (LPS/D-Gal)-induced liver injury. We have demonstrated that, in adult liver, LGR4 is expressed in hepatocytes and responds to Rspo1 with internalization. Rspo1 is responsive to various nutritional states and to mTOR signaling. Activation of LGR4 by Rspo1 significantly reduced tumor necrosis factor-α (TNFα)-induced cell death, and levels of NF-κB-p65 and caspase-3 in cultured hepatocytes. Knockdown of hepatic LGR4 rendered hepatocytes more vulnerable to TNFα-induced damage in cultured primary cells and in the setting of HIRI and LPS/D-Gal-induced liver injury. Rspo1 potentiated both basal and Wnt3a-induced stabilization of β-catenin. Disruption of β-catenin signaling reversed the protective effects of Rspo1 on TNFα-induced hepatocyte toxicity. LGR4 knockdown increased nuclear translocation of NF-κB-p65 in response to acute injury. Overexpression of IKKβ attenuated the protective effects of Rspo1 on TNFα-induced cell death. In conclusion, the Rspo1-LGR4 system represents a novel pathway for cytoprotection and modulation of stress-induced tissue damage. NEW & NOTEWORTHY Functional LGR4 is present in mature hepatocytes. R-spodin1 protects hepatocytes from tumor necrosis factor-α-induced cell death. Liver-specific knockdown of LGR4 renders liver more susceptible to acute injury. LGR4 protects hepatocytes from injury by inhibition of NF-κB signaling.
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.