In Vivo Consequence of Vitamin C Insufficiency in Liver Injury: Vitamin C Ameliorates T-Cell-Mediated Acute Liver Injury in Gulo(-/-) Mice
In Vivo Consequence of Vitamin C Insufficiency in Liver Injury: Vitamin C Ameliorates T-Cell-Mediated Acute Liver Injury in Gulo(-/-) Mice
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DOI：
10.1089/ars.2012.4756
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发表时间：
2013-12-10
影响因子：
6.6
通讯作者：
Lee, Wang Jae
中科院分区：
文献类型：
--
作者：
Bae, Seyeon;Cho, Chung-Hyun;Lee, Wang Jae
目的：L-抗坏血酸（维生素 C）不足被认为是发生肝病的主要危险因素之一。然而，其在体内的具体作用和相关机制尚不清楚。本研究的目的是探讨维生素C对Gulo(-/-)小鼠肝损伤的体内保护作用及其相关机制，这些小鼠由于缺乏维生素C合成必需的L-古洛糖酸内酯氧化酶(Gulo)而无法像人类一样合成维生素C。结果：当通过注射刀豆球蛋白A（Con A）诱导Gulo（-/-）小鼠肝损伤时，维生素C不足的Gulo（-/-）小鼠出现更广泛的肝损伤，并伴随着凋亡肝细胞数量的增加。此外，维生素C不足的Gulo(-/-)小鼠中促炎细胞因子（例如TNF-和IFN-）的血浆和肝脏水平比对照小鼠高得多。此外，维生素C不足的Gulo(-/-)小鼠中肝脏浸润T细胞数量的增加与肝脏IFN诱导因子(IP-10)水平的增加有关。尽管维生素 C 不足的 Gulo(-/-) 小鼠体内白细胞介素 22 (IL-22)（一种保肝细胞因子）含量较高，但肝细胞中 IL-22R 表达及其下游 STAT3 激活存在缺陷。创新：我们首先证明了维生素 C 通过调节过度免疫激活和维持 IL-22R 信号通路来预防肝脏疾病发展的新型体内作用机制。结论：这些结果表明，通过补充足够的维生素 C 可以预防由炎症引起的严重肝损伤。抗氧化剂。氧化还原信号。 19, 2040-2053。
Aim: l-ascorbic acid (vitamin C) insufficiency is considered one of the major risk factors for the development of liver disease. However, its specific effects and related mechanisms in vivo are largely unknown. The objective of this study was to investigate the in vivo protective role of vitamin C and its related mechanisms in liver injury with Gulo(-/-) mice that cannot synthesize vitamin C like humans due to the lack of l-gulonolactone--oxidase (Gulo), an essential enzyme for vitamin C synthesis. Results: When liver injury was induced in Gulo(-/-) mice by injection of concanavalin A (Con A), there was greater extensive liver damage accompanied by an increased number of apoptotic hepatocytes in vitamin C-insufficient Gulo(-/-) mice. Additionally, the plasma and hepatic levels of the proinflammatory cytokines, such as TNF- and IFN-, were much higher in the vitamin C-insufficient Gulo(-/-) mice than in the control mice. Moreover, increased numbers of liver-infiltrating T-cells in the vitamin C-insufficient Gulo(-/-) mice were related to the increased hepatic levels of IFN-inducible factor (IP-10). Although the vitamin C-insufficient Gulo(-/-) mice had higher amounts of interleukin-22 (IL-22), a hepatoprotective cytokine, a defect in IL-22R expression and its downstream STAT3 activation in hepatocytes were found. Innovation: We first demonstrate the novel in vivo action mechanisms of vitamin C on the prevention of disease development in the liver, through the regulation of excessive immune activation and maintenance of the IL-22R signaling pathways. Conclusion: These results suggest that severe liver damage induced by inflammation could be prevented by sufficient supplementation with vitamin C. Antioxid. Redox Signal. 19, 2040-2053.