The influence of Derlin⁃1 on non⁃alcoholic fatty liver disease
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摘要:
目的：探讨内质网相关降解蛋白1（endoplasmic reticulum correlative protein 1，Derlin-1）在非酒精性脂肪肝组织中的表达情况及其通过对蛋白激酶R样内质网激酶（protein kinase R-like ER kinase，PERK），即内质网应激中未折叠蛋白反应感受蛋白的影响，抑制非酒精性脂肪肝（non-alcoholic fatty liver disease，NAFLD）的发生机制。方法：通过免疫组织化学染色及Western bolt技术检测NAFLD小鼠肝脏组织中Derlin-1的表达；在HepG2细胞中利用质粒过表达Derlin-1，以Western blot技术检测其对内质网应激信号通路PERK的影响。结果：Derlin1在NAFLD肝组织中表达明显高于正常肝脏组织；过表达Derlin-1能抑制内质网应激信号通路的激活。结论：Derlin1在NAFLD肝组织的高表达提示其可能通过抑制内质网应激中未折叠蛋白反应感受蛋白PERK，减少内质网应激，阻止肝脏细胞脂肪变。
Abstract:
Objective：This study aims to investigate the endoplasmic reticulum correlative protein 1 （Derlin-1） expression in non-alcoholic fatty liver disease（NAFLD）and its effect on PERK（protein kinase R-like ER kinase）signal pathway to inhibit NAFLD. Methods：The expressin of Derlin-1 in liver tissues of NAFLD mice was detected by immuhistochemical staining and Western blotting. The over-expression of Derlin-1 in HepG2 cell was performed by plasmid vector transfection. Derlin-1 inhibits PERK pathway detected by Western blotting. Results：The expression of Derlin-1 in liver tissues of NAFLD mice was increased compared with that in nomal liver tissues. Overexression of Derlin-1 inhibited endoplasmic reticulum stress pathway activition. Conclusion：High expression of Derlin-1 in liver tissues of NAFLD pratients may play a critical role in decreasing endoplasmic reticulum stress and inhibiting liver cell pemelosis through inhibiting PERK expression.
