Tadeja Kuret (Author), Katja Lakota (Author), Saša Čučnik (Author), Vesna Jurčić (Author), Oliver Distler (Author), Žiga Rotar (Author), Alojzija Hočevar (Author), Snežna Sodin-Šemrl (Author), Mojca Frank (Author)

Abstract

In this study, we explored expression of microRNA (miR), miR-target genes and matrix remodelling molecules in temporal artery biopsies (TABs) from treatment-naïve patients with giant cell arteritis (GCA, n = 41) and integrated these analyses with clinical, laboratory, ultrasound and histological manifestations of GCA. NonGCA patients (n = 4) served as controls. GCA TABs exhibited deregulated expression of several miRs (miR-21-5p, -145-5p, -146a-5p, -146b-5p, -155-5p, 424-3p, -424-5p, -503-5p), putative miR-target genes (YAP1, PELI1, FGF2, VEGFA, KLF4) and matrix remodelling factors (MMP2, MMP9, TIMP1, TIPM2) with key roles in Toll-like receptor signaling, mechanotransduction and extracellular matrix biology. MiR-424-3p, -503-5p, KLF4, PELI1 and YAP1 were identified as new deregulated molecular factors in GCA TABs. Quantities of miR-146a-5p, YAP1, PELI1, FGF2, TIMP2 and MMP9 were particularly high in histologically positive GCA TABs with occluded temporal artery lumen. MiR-424-5p expression in TABs and the presence of facial or carotid arteritis on ultrasound were associated with vision disturbances in GCA patients. Correlative analysis of miR-mRNA quantities demonstrated a highly interrelated expression network of deregulated miRs and mRNAs in temporal arteries and identified KLF4 as a candidate target gene of deregulated miR-21-5p, -146a-5p and -155-5p network in GCA TABs. Meanwhile, arterial miR and mRNA expression did not correlate with constitutive symptoms and signs of GCA, elevated markers of systemic inflammation nor sonographic characteristics of GCA. Our study provides new insights into GCA pathophysiology and uncovers new candidate biomarkers of vision impairment in GCA.

Keywords

velikanski celični arteritis;mikroRNA;preoblikovanje arterij;giant cell arteritis;microRNA;arterial remodelling;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616-002
COBISS: 67607811 Link will open in a new window
ISSN: 1422-0067
Views: 106
Downloads: 48
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Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: velikanski celični arteritis;mikroRNA;preoblikovanje arterij;
Type (COBISS): Article
Pages: str. 1-19
Volume: ǂVol. ǂ22
Issue: ǂiss. ǂ12
Chronology: 2021
DOI: 10.3390/ijms22126520
ID: 14825825