Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells

Michael Eadon, Alexander Jacob, Patrick N. Cunningham, Richard J. Quigg, Joe G N Garcia, Jessy J. Alexander

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0·05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings.

Original languageEnglish (US)
Pages (from-to)363-373
Number of pages11
JournalImmunology
Volume143
Issue number3
DOIs
StatePublished - 2014

Fingerprint

MicroRNAs
Endothelial Cells
Central Nervous System Lupus Vasculitis
Brain
Blood-Brain Barrier
Anaphylatoxin C5a Receptor
Complement C5a
Complement Activation
Genomics
Serum
Systemic Lupus Erythematosus
Blood Proteins
Complement System Proteins
Apoptosis
Inflammation
Polymerase Chain Reaction
Genes
Therapeutics

Keywords

  • Brain
  • Complement
  • Endothelial cells
  • Inflammation
  • Lupus
  • MicroRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Eadon, M., Jacob, A., Cunningham, P. N., Quigg, R. J., Garcia, J. G. N., & Alexander, J. J. (2014). Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells. Immunology, 143(3), 363-373. https://doi.org/10.1111/imm.12314

Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells. / Eadon, Michael; Jacob, Alexander; Cunningham, Patrick N.; Quigg, Richard J.; Garcia, Joe G N; Alexander, Jessy J.

In: Immunology, Vol. 143, No. 3, 2014, p. 363-373.

Research output: Contribution to journalArticle

Eadon, M, Jacob, A, Cunningham, PN, Quigg, RJ, Garcia, JGN & Alexander, JJ 2014, 'Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells', Immunology, vol. 143, no. 3, pp. 363-373. https://doi.org/10.1111/imm.12314
Eadon, Michael ; Jacob, Alexander ; Cunningham, Patrick N. ; Quigg, Richard J. ; Garcia, Joe G N ; Alexander, Jessy J. / Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells. In: Immunology. 2014 ; Vol. 143, No. 3. pp. 363-373.
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