脂肪肝中自噬体的异位定位是肝再生的关键因素。

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Organogenesis Pub Date : 2019-01-01 Epub Date: 2019-07-06 DOI:10.1080/15476278.2019.1633872
Yoshihiro Matsumoto, Tomoharu Yoshizumi, Takeo Toshima, Kazuki Takeishi, Takasuke Fukuhara, Shinji Itoh, Toru Ikegami, Yuji Soejima, Masaki Mori
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引用次数: 6

摘要

自噬在肝脏再生中起着关键作用。然而,没有研究证实再生脂肪肝的自噬通量。本研究的目的是阐明自噬在脂肪肝再生中的动力学。在非酒精性脂肪性肝病(NAFLD)模型db/db脂肪小鼠中进行70%肝部分切除(PH)后,我们研究了肝脏体积的恢复和存活率。电镜下观察再生肝的组织学变化。db/db小鼠PH后7 d存活率为20%,显著低于对照组(P< 0.01)。db/db小鼠PH后48 h内肝脏再生明显受损(P< 0.05)。与对照组相比,db/db小鼠的增殖细胞核抗原(PCNA)阳性细胞数量和细胞周期标志物cyclins D、E和A的表达水平均较低。在再生肝脏中,与对照组相比,db/db小鼠LC3-II水平较高,但p62表达增加,自噬溶酶体蛋白水解标志物组织蛋白酶D表达降低。电镜显示,db/db小鼠肝再生过程中的自噬体主要位于脂滴中。我们的研究结果表明,与对照组相比,db/db小鼠中自噬体的不同定位导致脂肪肝肝脏再生受损。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration.

Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration.

Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration.

Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration.

Autophagy has a critical role in liver regeneration. However, no studies have demonstrated autophagic flux in the regenerating fatty liver. The aim of this study was to clarify the dynamics of autophagy in the regeneration of the fatty liver. Following 70% partial hepatectomy (PH) in db/db fatty mice, which is a non-alcoholic fatty liver disease (NAFLD) model, we investigated the survival rate and recovery of liver volume. Histological examination of the regenerating liver was examined using electron microscopy. The 7-day survival rate after PH in db/db mice was 20%, which was significantly lower than that in control mice (P< .01). Liver regeneration within 48 h after PH was significantly impaired in db/db mice (P< .05). The number of proliferating cell nuclear antigen (PCNA) positive cells and the expression levels of cell-cycle markers cyclins D, E, and A were lower in db/db mice compared with controls. In the regenerating liver, LC3-II level was higher in db/db mice, but p62 expression was increased and cathepsin D expression, a marker of autophagolysosome proteolysis, was decreased compared with controls. Additionally, electronic microscopy revealed that autophagosomes during liver regeneration in db/db mice were mainly located in lipid droplets. Our findings indicate that the different localization of autophagosomes in db/db mice compared with controls led to impairment of liver regeneration in the fatty liver.

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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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