Conditional knockout of heparin-binding epidermal growth factor-like growth factor in the liver accelerates carbon tetrachloride-induced liver injury in mice.
Conditional knockout of heparin-binding epidermal growth factor-like growth factor in the liver accelerates carbon tetrachloride-induced liver injury in mice.
复制标题
有条件地敲除肝脏中与肝素结合的表皮生长因子样生长因子会加速四氯化碳引起的小鼠肝损伤。
DOI：
10.1111/j.1872-034x.2012.01074.x
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发表时间：
2012
期刊：
影响因子：
4.2
通讯作者：
T.
中科院分区：
文献类型：
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作者：
Takemura;T.;YoshidaY.;Kiso;S.;Saji;Y.;Ezaki;H.;Hamano;M.;Kizu;T.;Egawa;M.; Chatani;N.;Furuta;K.;Kamada;Y.;Iwamoto;R.;Mekada;E.;Higashiyama;S.;Hayashi;N. and Takehara;T.
目的：我们之前证明了肝素结合表皮生长因子样生长因子（HB-EGF）在几种肝损伤中被诱导。由于HB‐EGF敲除（KO）小鼠在出生后立即死于子宫内或心脏缺陷，因此体内功能丧失研究有限。在这里，我们使用干扰素诱导型Mx-1启动子驱动的cre重组酶转基因产生肝脏特异性HB-EGF条件性敲除小鼠，并研究其在急性肝损伤中的作用。方法：我们通过单次腹腔注射四氯化碳（CCl 4）诱导HB-EGF KO小鼠和野生型小鼠的急性肝损伤，并通过生化和免疫组织化学分析评估肝损伤。结果：注射CCl 4后24 h，HB-EGF KO小鼠丙氨酸氨基转移酶水平显著升高，末端脱氧核苷酸转移酶dUTP缺口末端标记染色显示凋亡肝细胞数量显著增加。 我们还证明了HB‐EGF处理抑制肿瘤坏死因子-α-诱导的AML 12小鼠肝细胞凋亡，并促进这些细胞的伤口愈合反应。结论：本研究表明HB‐EGF在急性肝损伤中起保护作用。
Aim:We previously demonstrated that heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is induced in response to several liver injuries. Because the HB‐EGF knockout (KO) mice diein uteroor immediately after birth due to cardiac defects, the loss of function studyin vivois limited. Here, we generated liver‐specific HB‐EGF conditional knockout mice using the interferon‐inducible Mx‐1 promoter driven cre recombinase transgene and investigated its role during acute liver injury.Methods:We induced acute liver injury by a single i.p. injection of carbon tetrachloride (CCl4) in HB‐EGF KO mice and wild‐type mice and liver damage was assessed by biochemical and immunohistochemical analysis. We also used AML12 mouse hepatocyte cell lines to examine the molecular mechanism of HB‐EGF‐dependent anti‐apoptosis and wound‐healing process of the liverin vitro.Results:HB‐EGF KO mice exhibited a significant increase of alanine aminotransferase level and also showed a significant increase in the number of apoptotic hepatocytes assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining at 24 h after CCl4injection. We also demonstrated that HB‐EGF treatment inhibited tumor necrosis factor‐α‐induced apoptosis of AML12 mouse hepatocytes and promoted the wound‐healing response of these cells.Conclusion:This study showed that HB‐EGF plays a protective role during acute liver injury.