Graphene Oxide Causes Disordered Zonation Due to Differential Intralobular Localization in the Liver

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Graphene Oxide Causes Disordered Zonation Due to Differential Intralobular Localization in the Liver
	Wu, Yakun; Feng, Wenya; Liu, Rui; Xia, Tian; Liu, Sijin
刊名	ACS NANO
	2020-01
卷号	14 期号:1 页码:877-890
关键词	liver zonation zonated accumulation DNA methylation mRNA transcription graphene oxide
ISSN号	1936-0851
英文摘要	The liver is the primary organ to sequester nanodrugs, representing a substantial hurdle for drug delivery and raising toxicity concerns. However, the mechanistic details underlying the liver sequestration and effects on the liver are still elusive. The difficulty in studying the liver lies in its complexity, which is structured with stringently organized anatomical units called lobules. Graphene oxide (GO) has attracted attention for its applications in biomedicine, especially as a nanocarrier; however, its sequestration and effects in the liver, the major enrichment and metabolic organ, are less understood. Herein, we unveiled the differential distribution of GO in lobules in the liver, with a higher amount surrounding portal triad zones than the central vein zones. Strikingly, liver zonation patterns also changed, as reflected by changes in vital zonated genes involved in hepatocyte integrity and metabolism, leading to compromised hepatic functions. RNA-Seq and DNA methylation sequencing analyses unraveled that GO-induced changes in liver functional zonation could be ascribed to dysregulation of key signaling pathways governing liver zonation at not only mRNA transcriptions but also DNA methylation imprinting patterns, partially through TET-dependent signaling. Together, this study reveals the differential GO distribution pattern in liver lobules and pinpoints the genetic and epigenetic mechanisms in GO-induced liver zonation alterations.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/44700]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Wu, Yakun,Feng, Wenya,Liu, Rui,et al. Graphene Oxide Causes Disordered Zonation Due to Differential Intralobular Localization in the Liver[J]. ACS NANO,2020,14(1):877-890.
APA	Wu, Yakun,Feng, Wenya,Liu, Rui,Xia, Tian,&Liu, Sijin.(2020).Graphene Oxide Causes Disordered Zonation Due to Differential Intralobular Localization in the Liver.ACS NANO,14(1),877-890.
MLA	Wu, Yakun,et al."Graphene Oxide Causes Disordered Zonation Due to Differential Intralobular Localization in the Liver".ACS NANO 14.1(2020):877-890.