Thymosin β4 Prevents Oxidative Stress, Inflammation, and Fibrosis in Ethanol- and LPS-Induced Liver Injury in Mice.
Thymosin β4 Prevents Oxidative Stress, Inflammation, and Fibrosis in Ethanol- and LPS-Induced Liver Injury in Mice.
复制标题
DOI：
10.1155/2018/9630175
复制
发表时间：
2018
影响因子：
--
通讯作者：
Lakshman MR
中科院分区：
文献类型：
--
作者：
Shah R;Reyes-Gordillo K;Cheng Y;Varatharajalu R;Ibrahim J;Lakshman MR
胸腺素β 4（Tβ4）是一种肌动蛋白螯合蛋白，参与组织发育和再生。它可以预防多种组织的炎症和纤维化。本研究探讨了Tβ4在慢性乙醇和急性脂多糖（LPS）诱导的小鼠肝损伤中的作用。给C57 BL/6小鼠喂食含5%乙醇的液体饮食4周，并在有或没有LPS（2 mg/kg，腹膜内）的情况下灌胃乙醇（5 g/kg，管饲）6小时。腹腔注射Tβ4（1 mg/kg）1周。我们证明，Tβ4阻止乙醇和LPS介导的肝损伤标志物增加以及肝脏病理学变化。它还通过降低ROS和脂质过氧化作用以及增加抗氧化剂、还原型谷胱甘肽和锰依赖性超氧化物歧化酶来防止乙醇和LPS介导的氧化应激增加。它还通过阻断抑制蛋白IκB的磷酸化来防止核因子κ B的活化，从而防止促炎细胞因子的产生。此外，Tβ4通过抑制表观遗传阻遏物甲基-CpG结合蛋白2来预防纤维化，甲基-CpG结合蛋白2协同逆转过氧化物酶体增殖物激活受体-γ的表达并下调纤维化基因、血小板衍生生长因子-β受体、α-平滑肌肌动蛋白、胶原蛋白1和纤连蛋白，从而减少纤维化。我们的数据表明，Tβ4在酒精性肝损伤中具有抗氧化、抗炎和抗纤维化的潜力。
Thymosin beta 4 (Tβ4), an actin-sequestering protein, is involved in tissue development and regeneration. It prevents inflammation and fibrosis in several tissues. We investigated the role of Tβ4 in chronic ethanol- and acute lipopolysaccharide- (LPS-) induced mouse liver injury. C57BL/6 mice were fed 5% ethanol in liquid diet for 4 weeks plus binge ethanol (5 g/kg, gavage) with or without LPS (2 mg/kg, intraperitoneal) for 6 hours. Tβ4 (1 mg/kg, intraperitoneal) was administered for 1 week. We demonstrated that Tβ4 prevented ethanol- and LPS-mediated increase in liver injury markers as well as changes in liver pathology. It also prevented ethanol- and LPS-mediated increase in oxidative stress by decreasing ROS and lipid peroxidation and increasing the antioxidants, reduced glutathione and manganese-dependent superoxide dismutase. It also prevented the activation of nuclear factor kappa B by blocking the phosphorylation of the inhibitory protein, IκB, thereby prevented proinflammatory cytokine production. Moreover, Tβ4 prevented fibrogenesis by suppressing the epigenetic repressor, methyl-CpG-binding protein 2, that coordinately reversed the expression of peroxisome proliferator-activated receptor-γ and downregulated fibrogenic genes, platelet-derived growth factor-β receptor, α-smooth muscle actin, collagen 1, and fibronectin, resulting in reduced fibrosis. Our data suggest that Tβ4 has antioxidant, anti-inflammatory, and antifibrotic potential during alcoholic liver injury.
登录
查看更多内容
影响因子：
4.6
作者：
Kawaratani H;Tsujimoto T;Douhara A;Takaya H;Moriya K;Namisaki T;Noguchi R;Yoshiji H;Fujimoto M;Fukui H
通讯作者：
Fukui H
影响因子：
2.4
作者：
Hamesch, K.;Borkham-Kamphorst, E.;Weiskirchen, R.
通讯作者：
Weiskirchen, R.
DOI：
10.1111/j.1749-6632.2010.05483.x
发表时间：
2010-01-01
期刊：
THYMOSINS IN HEALTH AND DISEASE
影响因子：
--
作者：
Ehrlich, H. Paul;Hazard, Sprague W., III
通讯作者：
Hazard, Sprague W., III
影响因子：
4.2
作者：
Gopal, DV;Rosen, HR
通讯作者：
Rosen, HR
DOI：
10.1196/annals.1415.035
发表时间：
2007-01-01
期刊：
THYMOSINS IN HEALTH AND DISEASE: FIRST INTERNATIONAL SYMPOSIUM
影响因子：
--
作者：
Barnaeva, Elena;Nadezhda, Agladze;Rojkind, Marcos
通讯作者：
Rojkind, Marcos