检索结果-南通市图书馆

AB038. Pathological neovascularization in retinopathy of prematurity is regulated by heme-derived iron trafficking

Annals of Eye Science 2019年第1期 213-213页

作者： Tapan Agnihotri Nicholas Kim Gael Cagnone Jin Sung Kim Emilie Heckel Sheetal Pundir perrine gaub Florian Wunnemann Walter Szarek Hyman Schipper Jean-Sebastien Joyal Department of Pharmacology and Therapeutics McGill UniversityMontréalQCCanada Department of Pediatrics Pharmacology and OphthalmologyCHU Sainte-Justine Research CenterUniversitéde MontrealMontréalQCCanada Department of Chemistry Queen’s UniversityKingstonONCanada

Background:Retinopathy of prematurity(ROP)is an eye disease of the immature newborn characterized by pathological neovascularization(NV).ROP classically arises due to changes in oxygen availability in the ***,other factors,such as red blood cell(RBC)transfusion,independently contribute to disease *** molecules,rich in RBC,are the primary source of endogenous *** is metabolized by heme oxygenase(HO)into biliverdin,carbon monoxide,and ferrous *** iron levels stabilize hypoxia-inducible factor 1α(HIF1α),the main transcription factor of vascular endothelial growth factor(VEGF)that drives *** we investigate the role of heme metabolism in pathological ***:ROP was studied using the well-characterized oxygen-induced retinopathy(OIR)mouse ***-type(WT)pups are exposed to high oxygen concentrations(FiO275%)for 5 days,from the post-natal day(P)7 to 12,and subsequently returned to room air until retinal collection at P12,P14,&*** are then analyzed via single-cell RNAseq,RT-qPCR,western blot,Prussian blue staining,and immunostaining techniques to elucidate the effect of OIR on iron metabolism and *** OIR,we quantified vaso-obliteration(VO)and pathologic neovascular(NV)areas at P17 to assess the effects of1 Hmox1 competitive inhibition,and2Hmox1 allosteric ***:Iron trafficking genes across different retinal cell-types were upregulated in OIR,including CP,FTH1,IREB2,TF,and ***,Prussian blue staining suggests iron accumulation in retinal vessels exposed to ***1 mRNA(n=7,P<0.01 at P17)and protein expression(n=3,P<0.05)were increased 3.8-fold from P12 to *** and single-cell RNAseq confirmed that Hmox1 predominantly resides in retinal microglial *** and allosterically Hmox1 inhibition decreased NV by 15%(n=15,P=0.02)and 60%(n=5,P<0.01)***:Iron metabolism has seldom been explored in the context of *** microglial heme metabolis

关键词： Retinopathy of prematurity(ROP) iron metabolism microglia

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

***-cell transcriptomics identifies cell-specific signatures of pathological angiogenesis

引用

Annals of Eye Science 2019年第1期 215-215页

作者： Gael Cagnone Sheetal Pundir Nick Kim Emilie Heckel Jin Sung Kim perrine gaub Florian Wunnemann Piet van Vliet Severine Leclerc Gregor Andelfinger Sylvain Chemtob Jean-Sebastien Joyal CHU Ste-Justine Research Center Universitéde MontréalMontréalQCCanada Faculty of Medicine Department of Pharmacology and PhysiologyUniversitéde MontréalMontréalQCCanada Faculty of Medicine Department of PediatricsUniversity of MontrealUniversitéde MontréalMontréalQCCanada Department of Pharmacology and Therapeutics McGill UniversityMontréalQCCanada

Background:To treat vascular proliferative diseases,anti-VEGF therapies have shown systemic adverse effects attributable to the lack of selectivity between pathological and physiological ***,identifying the molecular mechanisms that are only specific to pathological cell types is crucial to develop better precision ***:Here,we used different cell type enrichment approaches combined with single-cell RNA sequencing to define the transcriptomic changes within each retinal cell types in a mouse model of ischemic *** retinal model develops pathological neovascularization(NV)in response to local hypoxia following oxygen-induced vessel obliteration(P7 to P12).The NV phenotype is characterized by the progressive appearance of vascular tufts resulting from misguided,abnormal proliferation of endothelial cells that we monitored at 3 consecutive time points-P12,P14 and P17(peak of NV).Results:By following the dynamic response to hypoxia,our experimental design reveals how pathological angiogenesis is specifically associated with significant metabolic adaptations in different subtypes of endothelial cells(i.e.,Tips vs Stalk cells).We also identify a pathological subtype of glial cells over-expressing VEGFA and pro-inflammatory IL-1 receptor *** subtype of activated glial cells was targeted using selective IL1R antagonist treatment which reduced glial activation,inflammation,NV and promotes physiological angiogenesis,therefore improving tissue ***:Our results illustrate how analyzing cell type heterogeneity in tissues developing pathological angiogenesis allows establishing better targeting therapies to restore vascular integrity.

关键词： Single-cell RNAseq angiogenesis pathological vascularization metabolism inflammation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：