Cellular fibronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury
Cellular fibronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury
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DOI：
10.4254/wjh.v3.i2.45
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发表时间：
2011-02-27
影响因子：
2.4
通讯作者：
Casey, Carol A.
中科院分区：
文献类型：
--
作者：
Aziz-Seible, Razia S.;McVicker, Benita L.;Casey, Carol A.
目的：研究酒精性损伤期间细胞纤连蛋白 (cFn) 积累的后果，并研究增加的 cFn 是否会通过产生可能导致酒精性肝损伤的因子而对肝细胞 (HC) 产生影响。 方法：从喂食对照或乙醇流质饮食 4 至 6 周的大鼠中分离 HC。向培养20小时的细胞中添加外源cFn（高达7.5μg/mL），观察活力（乳酸脱氢酶）、凋亡（半胱天冬酶活性）和促炎细胞因子（肿瘤坏死因子α、TNF-α和白细胞介素6、IL-6）、基质金属蛋白酶（MMP）及其分泌 抑制剂（金属蛋白酶组织抑制剂，TIMP）被确定。在 3 小时内测定制剂中碘化 cFn 的降解情况。结果：从喂食乙醇的动物中分离出的 HC 中，cFn 降解受到损害，导致其在基质中积累。添加外源性 cFn 不会影响对照或乙醇喂养动物的 HC 活力，并且仅在较高浓度时才会影响细胞凋亡。然而，外源添加的 cFn 会增加 MMP、TIMP、TNF-α 和 IL-6 的分泌，与对照组相比，来自乙醇喂养动物的 HC 表现出敏感性增加。 结论：这些结果表明，在酒精性肝损伤中观察到的 cFn 量升高可以刺激肝细胞产生促进进一步组织损伤的因子。 (C)2011年百事登。版权所有。
AIM: To examine the consequences of cellular fibronectin (cFn) accumulation during alcohol-induced injury, and investigate whether increased cFn could have an effect on hepatocytes (HCs) by producing factors that could contribute to alcohol-induced liver injury.METHODS: HCs were isolated from rats fed a control or ethanol liquid diet for four to six weeks. Exogenous cFn (up to 7.5 mu g/mL) was added to cells cultured for 20 h, and viability (lactate dehydrogenase), apoptosi (caspase activity) and secretion of proinflammatory cytokines (tumor necrosis factor alpha, TNF-alpha and interleukin 6, IL-6), matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) was determined. Degradation of iodinated cFn was determined over a 3 h time period in the preparations.RESULTS: cFn degradation is impaired in HCs isolated from ethanol-fed animals, leading to its accumulation in the matrix. Addition of exogenous cFn did not affect viability of HCs from control or ethanol-fed animals, and apoptosis was affected only at the higher concentration. Secretion of MMPs, TIMPs, TNF-alpha and IL-6, however, was increased by exogenously added cFn, with HCs from ethanol-fed animals showing increased susceptibility compared to the controls.CONCLUSION: These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage. (C) 2011 Baishideng. All rights reserved.