ArticleBioelectronic medicine2023
Hepatic stellate cell activation markers are regulated by the vagus nerve in systemic inflammation.
Article in Bioelectronic medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- NPY promotes macrophage polarization and hepatic fibrogenesis via PI3K/MAPK-dependent neuroimmune mechanisms.Cellular and molecular life sciences : CMLS · 2026Article
- Neuromodulation using Bioelectronics-enabled therapies to combat insulin resistance and its comorbidities.Journal of diabetes and metabolic disorders · 2026Review
- Neuroimmune Dynamics in Diseases of the Arterial Wall: Mechanistic Foundations and Translational Prospects.Current atherosclerosis reports · 2026Review
- Lymphocyte Antigen 6G Mediates Vagotomy-Associated Reduction in Body Weight.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Enhancing Liver Transplant Outcomes through Liver Precooling to Mitigate Inflammatory Response and Protect Mitochondrial Function.Biomedicines · 2024Article
- The brain-liver cholinergic anti-inflammatory pathway and viral infections.Bioelectronic medicine · 2023Review
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundThe liver is an important immunological organ and liver inflammation is part of the pathophysiology of non-alcoholic steatohepatitis, a condition that may promote cirrhosis, liver cancer, liver failure, and cardiovascular disease. Despite dense innervation of the liver parenchyma, little is known about neural regulation of liver function in inflammation. Here, we study vagus nerve control of the liver response to acute inflammation.
methodsMale C57BL/6 J mice were subjected to either sham surgery, surgical vagotomy, or electrical vagus nerve stimulation followed by intraperitoneal injection of the TLR2 agonist zymosan. Animals were euthanized and tissues collected 12 h after injection. Samples were analyzed by qPCR, RNAseq, flow cytometry, or ELISA.
resultsHepatic mRNA levels of pro-inflammatory mediators Ccl2, Il-1β, and Tnf-α were significantly higher in vagotomized mice compared with mice subjected to sham surgery. Differences in liver Ccl2 levels between treatment groups were largely reflected in the plasma chemokine (C-C motif) ligand 2 (CCL2) concentration. In line with this, we observed a higher number of macrophages in the livers of vagotomized mice compared with sham as measured by flow cytometry. In mice subjected to electrical vagus nerve stimulation, hepatic mRNA levels of Ccl2, Il1β, and Tnf-α, and plasma CCL2 levels, were significantly lower compared with sham. Interestingly, RNAseq revealed that a key activation marker for hepatic stellate cells (HSC), Pnpla3, was the most significantly differentially expressed gene between vagotomized and sham mice. Of note, several HSC-activation associated transcripts were higher in vagotomized mice, suggesting that signals in the vagus nerve contribute to HSC activation. In support of this, we observed significantly higher number of activated HSCs in vagotomized mice as compared with sham as measured by flow cytometry.
conclusionsSignals in the cervical vagus nerve controlled hepatic inflammation and markers of HSC activation in zymosan-induced peritonitis.
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