MicroRNA signature of human microvascular endothelium infected with Rickettsia rickettsii

Abha Sahni, Hema P. Narra, Jignesh Patel, Sanjeev Sahni

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number1471
JournalInternational Journal of Molecular Sciences
Volume18
Issue number7
DOIs
StatePublished - Jul 9 2017

Fingerprint

Rickettsia rickettsii
endothelium
Endothelial cells
MicroRNAs
Endothelium
infectious diseases
signatures
genes
Genes
Cell signaling
Gene encoding
fever
Rocky Mountains (North America)
Microarrays
Gene expression
pathogenesis
gene expression
destabilization
Demonstrations
Endothelial Cells

Keywords

  • Endothelial cells
  • Microarray
  • MicroRNAs
  • NOTCH1
  • Rickettsia rickettsii

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

MicroRNA signature of human microvascular endothelium infected with Rickettsia rickettsii. / Sahni, Abha; Narra, Hema P.; Patel, Jignesh; Sahni, Sanjeev.

In: International Journal of Molecular Sciences, Vol. 18, No. 7, 1471, 09.07.2017.

Research output: Contribution to journalArticle

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