PDZK1 gene transfer ameliorates lipopolysaccharide-induced cholestasis in rats by rescuing hepatic ABC transporters.

IF 1.3 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioscience, Biotechnology, and Biochemistry Pub Date : 2025-02-20 DOI:10.1093/bbb/zbae190

Tao Wu, Ji Wu, Li Liu, Hongping Song

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Abstract

Lipopolysaccharide (LPS) causes inflammatory cholestasis in sepsis. We investigated the role of PDZK1 in the repression of ABC transporters in LPS-induced cholestasis. Lentiviral gene transfer of PDZK1 to rats was conducted to explore its influence on cholestasis induced by LPS. And the effect of lentivirus-mediated shRNA targeting PDZK1 on ABC transporters in rat liver BRL-3A cells was evaluated. Lentiviral vector encoding rat PDZK1 was administered to rats by tail intravenous injection. Obviously elevated serum total bile acid level and liver biochemical markers in cholestatic rats were decreased by the Lv-PDZK1 delivery. Also, Lv-PDZK1 delivery stimulated the suppressed hepatic ABC transporters expression. In vitro, after the lentiviral vector LV3/PDZK1 shRNA transfection, no expression of PDZK1 and mild expression of ABC transporters were detected in BRL-3A cells by Western blotting. Our results indicate that the lentiviral-mediated hepatocyte PDZK1 expression ameliorates LPS-induced cholestasis in rats by rescuing hepatic ABC transporters expression.

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PDZK1基因转移通过挽救肝ABC转运体改善脂多糖诱导的大鼠胆汁淤积。

脂多糖（LPS）引起脓毒症的炎症性胆汁淤积。我们研究了PDZK1在lps诱导的胆汁淤积中抑制ABC转运蛋白的作用。采用慢病毒将PDZK1基因转染大鼠，探讨其对LPS诱导的胆汁淤积的影响。并评价慢病毒介导的靶向PDZK1 shRNA对大鼠肝脏BRL-3A细胞ABC转运蛋白的影响。将编码大鼠PDZK1的慢病毒载体尾静脉给药。给药后血清总胆汁酸（TBA）水平和肝脏生化指标均明显降低。此外，Lv-PDZK1的递送也刺激了被抑制的肝脏ABC转运蛋白的表达。体外，慢病毒载体LV3/PDZK1 shRNA转染后，Western blotting检测BRL-3A细胞中PDZK1无表达，ABC转运蛋白轻度表达。我们的研究结果表明，慢病毒介导的肝细胞PDZK1表达通过挽救肝ABC转运蛋白的表达来改善lps诱导的大鼠胆汁淤积。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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阿拉丁

Lipopolysaccharide

阿拉丁

Lipopolysaccharide

阿拉丁

Lipopolysaccharide

来源期刊

Bioscience, Biotechnology, and Biochemistry 生物-生化与分子生物学

CiteScore

3.50

自引率

0.00%

发文量

183

审稿时长

1 months

期刊介绍： Bioscience, Biotechnology, and Biochemistry publishes high-quality papers providing chemical and biological analyses of vital phenomena exhibited by animals, plants, and microorganisms, the chemical structures and functions of their products, and related matters. The Journal plays a major role in communicating to a global audience outstanding basic and applied research in all fields subsumed by the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA).