Cargando…

MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii

MicroRNAs (miRNAs) mediate gene silencing by destabilization and/or translational repression of target mRNA. Infection of human microvascular endothelial cells as primary targets of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, triggers host responses appertaining to al...

Descripción completa

Detalles Bibliográficos
Autores principales: Sahni, Abha, Narra, Hema P., Patel, Jignesh, Sahni, Sanjeev K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535962/
https://www.ncbi.nlm.nih.gov/pubmed/28698491
http://dx.doi.org/10.3390/ijms18071471
_version_ 1783253934882684928
author Sahni, Abha
Narra, Hema P.
Patel, Jignesh
Sahni, Sanjeev K.
author_facet Sahni, Abha
Narra, Hema P.
Patel, Jignesh
Sahni, Sanjeev K.
author_sort Sahni, Abha
collection PubMed
description MicroRNAs (miRNAs) mediate gene silencing by destabilization and/or translational repression of target mRNA. Infection of human microvascular endothelial cells as primary targets of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, triggers host responses appertaining to alterations in cellular gene expression. Microarray-based profiling of endothelial cells infected with R. rickettsii for 3 or 24 h revealed differential expression of 33 miRNAs, of which miRNAs129-5p, 200a-3p, 297, 200b-3p, and 595 were identified as the top five up-regulated miRNAs (5 to 20-fold, p ≤ 0.01) and miRNAs 301b-3p, 548a-3p, and 377-3p were down-regulated (2 to 3-fold, p ≤ 0.01). Changes in the expression of selected miRNAs were confirmed by q-RT-PCR in both in vitro and in vivo models of infection. As potential targets, expression of genes encoding NOTCH1, SMAD2, SMAD3, RIN2, SOD1, and SOD2 was either positively or negatively regulated. Using a miRNA-specific mimic or inhibitor, NOTCH1 was determined to be a target of miRNA 200a-3p in R. rickettsii-infected human dermal microvascular endothelial cells (HMECs). Predictive interactome mapping suggested the potential for miRNA-mediated modulation of regulatory gene networks underlying important host cell signaling pathways. This first demonstration of altered endothelial miRNA expression provides new insights into regulatory elements governing mechanisms of host responses and pathogenesis during human rickettsial infections.
format Online
Article
Text
id pubmed-5535962
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-55359622017-08-04 MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii Sahni, Abha Narra, Hema P. Patel, Jignesh Sahni, Sanjeev K. Int J Mol Sci Article MicroRNAs (miRNAs) mediate gene silencing by destabilization and/or translational repression of target mRNA. Infection of human microvascular endothelial cells as primary targets of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, triggers host responses appertaining to alterations in cellular gene expression. Microarray-based profiling of endothelial cells infected with R. rickettsii for 3 or 24 h revealed differential expression of 33 miRNAs, of which miRNAs129-5p, 200a-3p, 297, 200b-3p, and 595 were identified as the top five up-regulated miRNAs (5 to 20-fold, p ≤ 0.01) and miRNAs 301b-3p, 548a-3p, and 377-3p were down-regulated (2 to 3-fold, p ≤ 0.01). Changes in the expression of selected miRNAs were confirmed by q-RT-PCR in both in vitro and in vivo models of infection. As potential targets, expression of genes encoding NOTCH1, SMAD2, SMAD3, RIN2, SOD1, and SOD2 was either positively or negatively regulated. Using a miRNA-specific mimic or inhibitor, NOTCH1 was determined to be a target of miRNA 200a-3p in R. rickettsii-infected human dermal microvascular endothelial cells (HMECs). Predictive interactome mapping suggested the potential for miRNA-mediated modulation of regulatory gene networks underlying important host cell signaling pathways. This first demonstration of altered endothelial miRNA expression provides new insights into regulatory elements governing mechanisms of host responses and pathogenesis during human rickettsial infections. MDPI 2017-07-09 /pmc/articles/PMC5535962/ /pubmed/28698491 http://dx.doi.org/10.3390/ijms18071471 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sahni, Abha
Narra, Hema P.
Patel, Jignesh
Sahni, Sanjeev K.
MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii
title MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii
title_full MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii
title_fullStr MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii
title_full_unstemmed MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii
title_short MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii
title_sort microrna signature of human microvascular endothelium infected with rickettsia rickettsii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535962/
https://www.ncbi.nlm.nih.gov/pubmed/28698491
http://dx.doi.org/10.3390/ijms18071471
work_keys_str_mv AT sahniabha micrornasignatureofhumanmicrovascularendotheliuminfectedwithrickettsiarickettsii
AT narrahemap micrornasignatureofhumanmicrovascularendotheliuminfectedwithrickettsiarickettsii
AT pateljignesh micrornasignatureofhumanmicrovascularendotheliuminfectedwithrickettsiarickettsii
AT sahnisanjeevk micrornasignatureofhumanmicrovascularendotheliuminfectedwithrickettsiarickettsii