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

Povzetek

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.

Ključne besede

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

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL MF - Medicinska fakulteta
UDK: 616-002
COBISS: 67607811 Povezava se bo odprla v novem oknu
ISSN: 1422-0067
Št. ogledov: 106
Št. prenosov: 48
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: velikanski celični arteritis;mikroRNA;preoblikovanje arterij;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-19
Letnik: ǂVol. ǂ22
Zvezek: ǂiss. ǂ12
Čas izdaje: 2021
DOI: 10.3390/ijms22126520
ID: 14825825