Skip to main content
main-content

01.12.2016 | Research article | Ausgabe 1/2016 Open Access

Arthritis Research & Therapy 1/2016

Sjögren’s syndrome-associated microRNAs in CD14+ monocytes unveils targeted TGFβ signaling

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 1/2016
Autoren:
Adrienne E. G. Williams, Kevin Choi, Annie L. Chan, Yun Jong Lee, Westley H. Reeves, Michael R. Bubb, Carol M. Stewart, Seunghee Cha
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13075-016-0987-0) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

AEGW contributed to the experimental design, acquisition of the data set, analysis and interpretation of the work presented, and drafting and revision of the manuscript. KC acquired the data from qRT-PCR and assisted drafting the manuscript. YL contributed to data interpretation and manuscript revision. ALC, WHR, and MRB made contributions to study design, and acquisition of clinical data. CMS contributed to the design of the study. SC made substantial contributions to the study’s conception and design, coordination, drafting and revision of the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Sjögren’s syndrome (SjS) monocytes have a pro-inflammatory phenotype, which may influence SjS pathogenesis. MicroRNAs (miRNAs) are small endogenously expressed molecules that can inhibit protein expression of their targeted genes and have important functions in regulating cell signaling responses. We profiled miRNAs in SjS monocytes to identify a SjS-specific miRNA profile and determine the potential roles of miRNAs in SjS pathogenesis.

Methods

Total RNA was extracted from healthy control (HC, n = 10), SjS (n = 18), systemic lupus erythematosus (SLE, n = 10), and rheumatoid arthritis (RA, n = 10) peripheral blood CD14+ monocytes for miRNA microarray analysis. To validate select miRNAs from the microarray analysis, the original cohort and a new cohort of monocyte RNA samples from HC (n = 9), SjS (n = 12), SLE (n = 8), and RA (n = 9) patients were evaluated by quantitative reverse transcription (RT)-PCR. Functional predictions of differentially expressed miRNAs were determined through miRNA target prediction database analyses. Statistical analyses performed included one-way analysis of variance with Bonferroni post tests, linear regression, and receiver operating characteristic curve analyses.

Results

MiRNAs were predominantly upregulated in SjS monocytes in comparison with controls. Quantitative RT-PCR confirmations supported co-regulation of miR-34b-3p, miR-4701-5p, miR-609, miR-300, miR-3162-3p, and miR-877-3p in SjS monocytes (13/30, 43.3 %) in comparison with SLE (1/17, 5.8 %) and RA (1/18, 5.6 %). MiRNA-target pathway predictions identified SjS-associated miRNAs appear to preferentially target the canonical TGFβ signaling pathway as opposed to pro-inflammatory interleukin-12 and Toll-like receptor/NFkB pathways.

Conclusions

Our results underscore a novel underlying molecular mechanism where SjS-associated miRNAs may collectively suppress TGFβ signaling as opposed to pro-inflammatory interleukin-12 and Toll-like receptor/NFκB pathways in SjS pathogenesis.
Zusatzmaterial
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2016

Arthritis Research & Therapy 1/2016 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise