Gut dysbiosis-derived exosomes trigger hepatic steatosis by transiting HMGB1 from intestinal to liver in mice
Gut dysbiosis-derived exosomes trigger hepatic steatosis by transiting HMGB1 from intestinal to liver in mice
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DOI：
10.1016/j.bbrc.2018.12.180
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发表时间：
2019-02-12
影响因子：
3.1
通讯作者：
Zhi, Fachao
中科院分区：
文献类型：
--
作者：
Chen, Yu;Sun, Huanhuan;Zhi, Fachao
在过去的十年中，关于肠 - 肝轴生物学的研究有助于理解非酒精性脂肪性肝病（NAFLD）的基础生物学。高迁移率族蛋白B1（HMGB1）作为一种关键的损伤相关分子，与肝脏脂肪变性的程度呈现显著相关性。然而，其潜在的分子机制仍不清楚。在当前对高脂肪饮食（HFD）喂养的ASC（ - / - ）小鼠的研究中，我们通过16S rDNA测序检测到肠道微生物群紊乱，厚壁菌门与拟杆菌门的比例以及链霉菌数量异常增加。因此，我们对肠黏膜损伤进行了研究，并分析了NAFLD活动评分，发现ASC（ - / - ） - HFD组比其他组受损更严重。此外，HMGB1在肠道组织中显著增加，并与外泌体标记物共定位。我们发现ASC（ - / - ） - HFD组的外泌体中HMGB1显著升高。它通过外泌体从肠道运输到肝脏，从而在菌群失调时引发肝脏脂肪变性。总之，研究结果表明HMGB1在肠 - 肝轴机制中起着至关重要的作用。（C）2019爱思唯尔公司。保留所有权利。
In the past decade, research on the biology of the gut-liver axis has assisted in understanding the basic biology of nonalcoholic fatty liver disease (NAFLD). High mobility group box 1 (HMGB1) protein, in its role as a crucial injury-related molecule, displays a substantial correlation with the degree of liver steatosis. However, its underlying molecular mechanism remains unclear. In the current study of ASC(-/-) mice on a high-fat diet (HFD), we observed disorder of the gut microbiota along with abnormal increases in the Firmicutes:Bacteroidetes ratio and in Streptomyces, both of which were detected by 16S rDNA sequencing. Therefore, we investigated the intestinal mucosal injury and analyzed the NAFLD activity score and found that the ASC(-/-)-HFD group was more severely impaired than the others. Moreover, HMGB1 increased significantly in the intestinal tissue and was co-localized with an exosomal marker. We revealed that HMGB1 was significantly elevated in the exosomes of the ASC(-/-)-HFD group. It transported by exosomes from the intestine to the liver, thereby triggering hepatic steatosis when dysbiosis. In conclusion, the findings indicated that HMGB1 plays a crucial role in the gut-liver axis mechanism. (C) 2019 Elsevier Inc. All rights reserved.