通过单细胞转录组学剖析马兜铃酸诱导肝毒性的细胞和分子机制

IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
ACS Applied Materials & Interfaces Pub Date : 2022-09-22 eCollection Date: 2022-12-01 DOI:10.1093/pcmedi/pbac023
Piao Luo, Jiayun Chen, Qian Zhang, Fei Xia, Chen Wang, Yunmeng Bai, Huan Tang, Dandan Liu, Liwei Gu, Qingfeng Du, Wei Xiao, Chuanbin Yang, Jigang Wang
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引用次数: 0

摘要

背景:马兜铃酸(AAs)是马兜铃科植物Aristolochia和Asarum的一类致癌和致突变天然产物,众所周知可诱发肾毒性和尿道癌。方法:在此,我们旨在利用先进的单细胞 RNA 测序(scRNA-seq)和蛋白质组学技术,剖析马兜铃酸 I(AAI)诱导肝毒性的潜在细胞和分子机制。我们首次建立了小鼠肝脏对 AAI 反应的单细胞图谱:结果:在肝细胞中,我们的研究结果表明,AAI激活了NF-κB和STAT3信号通路,这可能有助于炎症反应和细胞凋亡。在肝窦状内皮细胞(LSECs)中,AAI激活了多种氧化应激和炎症相关信号通路,并诱导细胞凋亡。重要的是,AAI诱导细胞毒性T细胞浸润,激活肝脏中的促炎症巨噬细胞和中性粒细胞,产生炎症细胞因子,从而加重炎症:总之,我们的研究在单细胞水平上提供了有关AAs诱导的肝毒性分子特征的新知识,并为AAs相关肝毒性的未来治疗方案提供了建议。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Dissection of cellular and molecular mechanisms of aristolochic acid-induced hepatotoxicity via single-cell transcriptomics.

Dissection of cellular and molecular mechanisms of aristolochic acid-induced hepatotoxicity via single-cell transcriptomics.

Dissection of cellular and molecular mechanisms of aristolochic acid-induced hepatotoxicity via single-cell transcriptomics.

Dissection of cellular and molecular mechanisms of aristolochic acid-induced hepatotoxicity via single-cell transcriptomics.

Background: Aristolochic acids (AAs), a class of carcinogenic and mutagenic natural products from Aristolochia and Asarum plants, are well-known to be responsible for inducing nephrotoxicity and urothelial carcinoma. Recently, accumulating evidence suggests that exposure to AAs could also induce hepatotoxicity and even hepatocellular carcinoma, though the mechanisms are poorly defined.

Methods: Here, we aimed to dissect the underlying cellular and molecular mechanisms of aristolochic acid I (AAI)-induced hepatotoxicity by using advanced single-cell RNA sequencing (scRNA-seq) and proteomics techniques. We established the first single-cell atlas of mouse livers in response to AAI.

Results: In hepatocytes, our results indicated that AAI activated NF-κB and STAT3 signaling pathways, which may contribute to the inflammatory response and apoptosis. In liver sinusoidal endothelial cells (LSECs), AAI activated multiple oxidative stress and inflammatory associated signaling pathways and induced apoptosis. Importantly, AAI induced infiltration of cytotoxic T cells and activation of proinflammatory macrophage and neutrophil cells in the liver to produce inflammatory cytokines to aggravate inflammation.

Conclusions: Collectively, our study provides novel knowledge of AAs-induced molecular characteristics of hepatotoxicity at a single-cell level and suggests future treatment options for AAs associated hepatotoxicity.

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来源期刊
ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces 工程技术-材料科学:综合
CiteScore
16.00
自引率
6.30%
发文量
4978
审稿时长
1.8 months
期刊介绍: ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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