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Liver Vitronectin Release into the Bloodstream Increases Due to Reduced Vagal Muscarinic Signaling After Cerebral Stroke in Female Mice

Overview
Journal Physiol Rep
Specialty Physiology
Date 2022 May 9
PMID 35531929
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Abstract

Vitronectin (VTN) is a glycoprotein enriched in the blood and activates integrin receptors. VTN blood levels increase only in female mice 24 h after an ischemic stroke and exacerbate brain injury through IL-6-driven inflammation, but the VTN induction mechanism is unknown. Here, a 30 min middle cerebral artery occlusion (MCAO) in female mice induced VTN protein in the liver (normally the main source) in concert with plasma VTN. Male mice were excluded as VTN is not induced after stroke. MCAO also increased plasma VTN levels after de novo expression of VTN in the liver of VTN female mice, using a hepatocyte-specific (SERPINA1) promoter. MCAO did not affect SERPINA1 or VTN mRNA in the liver, brain, or several peripheral organs, or platelet VTN, compared to sham mice. Thus, hepatocytes are the source of stroke-induced increases in plasma VTN, which is independent of transcription. The cholinergic innervation by the parasympathetic vagus nerve is a potential source of brain-liver signaling after stroke. Right-sided vagotomy at the cervical level led to increased plasma VTN levels, suggesting that VTN release is inhibited by vagal tone. Co-culture of hepatocytes with cholinergic neurons or treatment with acetylcholine, but not noradrenaline (sympathetic transmitter), suppressed VTN expression. Hepatocytes have muscarinic receptors and the M1/M3 agonist bethanechol decreased VTN mRNA and protein release in vitro via M1 receptors. Finally, systemic bethanechol treatment blocked stroke-induced plasma VTN. Thus, VTN translation and release are inhibited by muscarinic signaling from the vagus nerve and presents a novel target for lessening detrimental VTN expression.

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Pan W, Xiang L, Liang X, Du W, Zhao J, Zhang S Mediators Inflamm. 2023; 2023:6623329.

PMID: 37501933 PMC: 10371469. DOI: 10.1155/2023/6623329.


Liver vitronectin release into the bloodstream increases due to reduced vagal muscarinic signaling after cerebral stroke in female mice.

Keasey M, Lovins C, Jia C, Hagg T Physiol Rep. 2022; 10(9):e15301.

PMID: 35531929 PMC: 9082388. DOI: 10.14814/phy2.15301.

References
1.
Holloway M, Cui Y, Laz E, Hosui A, Hennighausen L, Waxman D . Loss of sexually dimorphic liver gene expression upon hepatocyte-specific deletion of Stat5a-Stat5b locus. Endocrinology. 2007; 148(5):1977-86. PMC: 3282149. DOI: 10.1210/en.2006-1419. View

2.
Loiler S, Conlon T, Song S, Tang Q, Warrington K, Agarwal A . Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver. Gene Ther. 2003; 10(18):1551-8. DOI: 10.1038/sj.gt.3302046. View

3.
Carreiras F, Denoux Y, Staedel C, Lehmann M, Sichel F, Gauduchon P . Expression and localization of alpha v integrins and their ligand vitronectin in normal ovarian epithelium and in ovarian carcinoma. Gynecol Oncol. 1996; 62(2):260-7. DOI: 10.1006/gyno.1996.0225. View

4.
Cunningham S, Alexander I . AAV-Mediated Gene Delivery to the Mouse Liver. Methods Mol Biol. 2019; 1937:213-219. DOI: 10.1007/978-1-4939-9065-8_12. View

5.
Lautt W . Afferent and efferent neural roles in liver function. Prog Neurobiol. 1983; 21(4):323-48. DOI: 10.1016/0301-0082(83)90016-3. View