About: AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways

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About: AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways
Creator	Lin, Ru Li, Qiuhong Chen, Zihe Fu, Xinyu Lei, Bo Lei, Chunyan Li, Hongwei Qiu, Yiguo Tao, Lifei Wang, Jiaming Zheng, Shijie
Source	PMC
abstract	Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1–7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1–7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1–7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases.
has issue date	2016-08-25(xsd:dateTime)
bibo:doi	10.1038/srep31912
bibo:pmid	27558087
has license	cc-by
sha1sum (hex)	4321e11dba137d5cb9785de364d8f972ac4bbec9
schema:url	https://doi.org/10.1038/srep31912
resource representing a document's title	AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways
has PubMed Central identifier	PMC4997264
has PubMed identifier	27558087
schema:publication	Sci Rep
resource representing a document's body	covid:4321e11dba137d5cb9785de364d8f972ac4bbec9#body_text
is schema:about of	named entity 'activity' named entity 'Mas' named entity 'inflammation' named entity 'ACE2' named entity 'ACE' named entity 'RAS' named entity 'Th1' named entity 'systemic' named entity 'STUDIES' named entity 'AAV' named entity 'OCULAR' named entity 'ACTIVATING' named entity 'INVESTIGATED' named entity 'EXPRESSION' named entity 'ACTIVATION' covid:arg/4321e11dba137d5cb9785de364d8f972ac4bbec9 named entity 'differentiation' named entity 'With' named entity 'inflammatory' named entity 'refractory' named entity 'axis' named entity 'vector' named entity 'enhancing' named entity 'immune responses' named entity 'signaling pathways' named entity 'MAPK' named entity 'immune responses' named entity 'STAT3' named entity 'molecular mechanisms' named entity 'Th17 cells' named entity 'ocular inflammation' named entity 'NF-κB' named entity 'ACE2' named entity 'ACE2' named entity 'RAS' named entity 'AT1R' named entity 'macrophages' named entity 'refractory' named entity 'signaling pathways' named entity 'ACE2' named entity 'MAPK' named entity 'Th1' named entity 'immune responses' named entity 'immune responses' named entity 'Uveitis' named entity 'actin' named entity 'MAPK' named entity 'intracellular' named entity 'ERK' named entity 'ERK1/2' named entity 'IFN-γ' named entity 'cornea' named entity '0.01' named entity 'gene delivery' named entity 'ACE2' named entity 'down-regulation' named entity 'inflammatory responses' named entity 'renin' named entity 'AAV' named entity 'PBS' named entity 'immunization' named entity 'retina' named entity 'anesthetized' named entity 'uveitis' named entity 'ACE2' named entity 'vector' named entity 'animal models' named entity 'Cupertino' named entity 'mice' named entity 'subretinal' named entity 'phenotype'

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