Liver vitronectin release into the bloodstream increases due to reduced vagal muscarinic signaling after cerebral stroke in female mice.
Liver vitronectin release into the bloodstream increases due to reduced vagal muscarinic signaling after cerebral stroke in female mice.
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DOI：
10.14814/phy2.15301
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发表时间：
2022-05
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
--
作者：
玻连蛋白（VTN）是一种在血液中富集的糖蛋白，可激活整合素受体。在缺血性脑卒中24小时后，只有雌性小鼠的VTN血液水平升高，并通过白细胞介素 - 6驱动的炎症加重脑损伤，但VTN的诱导机制尚不清楚。在此，雌性小鼠大脑中动脉闭塞（MCAO）30分钟会诱导肝脏（通常是主要来源）中的VTN蛋白与血浆VTN协同变化。由于雄性小鼠在脑卒中后VTN不会被诱导，所以将其排除在外。使用肝细胞特异性（SERPINA1）启动子在VTN - / - 雌性小鼠肝脏中重新表达VTN后，MCAO也会使血浆VTN水平升高。与假手术小鼠相比，MCAO不影响肝脏、大脑或几个外周器官中的SERPINA1或VTN mRNA，也不影响血小板VTN。因此，肝细胞是脑卒中诱导的血浆VTN升高的来源，且这一过程不依赖于转录。副交感迷走神经的胆碱能神经支配是脑卒中后脑 - 肝信号传导的一个潜在来源。在颈部水平进行右侧迷走神经切断术会导致血浆VTN水平升高，这表明VTN的释放受到迷走神经张力的抑制。肝细胞与胆碱能神经元共培养或用乙酰胆碱处理（而非去甲肾上腺素，交感神经递质）可抑制VTN表达。肝细胞具有毒蕈碱受体，M1/M3激动剂氨甲酰甲胆碱通过M1受体在体外降低VTN mRNA和蛋白质的释放。最后，全身性氨甲酰甲胆碱治疗可阻断脑卒中诱导的血浆VTN。因此，VTN的翻译和释放受到来自迷走神经的毒蕈碱信号的抑制，这为减少有害的VTN表达提供了一个新的靶点。
基西等人表明，雌性小鼠缺血性脑卒中后血浆玻连蛋白的升高是由肝脏释放产生的。他们表明，迷走神经通过毒蕈碱M1/3受体抑制玻连蛋白的产生，并且可以通过全身性氨甲酰甲胆碱治疗来阻断。这些发现与以有害的玻连蛋白水平为特征的疾病相关。
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. Keasey et al., show that an increase in plasma vitronectin after ischemic stroke in female mice is produced by release from the liver. They show that vitronectin production is inhibited by the vagus nerve through muscarinic M1/3 receptors and can be blocked by systemic treatment with bethanechol. These findings are relevant to diseases characterized by detrimental vitronectin levels.
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缺血性中风中的迷走神经刺激：新瓶中的旧酒。
影响因子：
3.4
作者：
Cai PY;Bodhit A;Derequito R;Ansari S;Abukhalil F;Thenkabail S;Ganji S;Saravanapavan P;Shekar CC;Bidari S;Waters MF;Hedna VS
通讯作者：
Hedna VS
影响因子：
2.9
作者：
Blouse, Grant E.;Dupont, Daniel M.;Andreasen, Peter A.
通讯作者：
Andreasen, Peter A.
影响因子：
4.7
作者：
Carreiras, F;Denoux, Y;Gauduchon, P
通讯作者：
Gauduchon, P
DOI：
10.1161/circinterventions.108.795799
发表时间：
2009-02-01
影响因子：
5.6
作者：
Derer, Wolfgang;Barnathan, Elliot S.;Dechend, Ralf
通讯作者：
Dechend, Ralf
影响因子：
8.3
作者：
Dawson J;Pierce D;Dixit A;Kimberley TJ;Robertson M;Tarver B;Hilmi O;McLean J;Forbes K;Kilgard MP;Rennaker RL;Cramer SC;Walters M;Engineer N
通讯作者：
Engineer N