20.500.12556/RUL-135649 Dysregulated expression of arterial microRNAs and their target gene networks in temporal arteries of treatment-naïve patients with giant cell arteritis 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. giant cell arteritis microRNA arterial remodelling microRNA-target genes toll-like receptor signaling arterial ultrasound vision disturbances velikanski celični arteritis mikroRNA preoblikovanje arterij true false true Angleški jezik Slovenski jezik Članek v reviji 2022-03-23 13:57:10 2022-03-23 13:57:17 2022-09-14 04:14:27 0000-00-00 00:00:00 2021 0 0 19 str. iss. 12, art. 6520 Vol. 22 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-002 1422-0067 10.3390/ijms22126520 67607811 RAZ_Kuret_Tadeja_2021.pdf RAZ_Kuret_Tadeja_2021.pdf 1 11AADE74B0B487AA71ADB13BCDAFECE8 a01322b11096178d440a0d9ca53f569e6e6a7b938dc86a4277789b7f3faa71b7 1cbc25d0-aaa9-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154857 https://www.mdpi.com/1422-0067/22/12/6520 0 c3076fdc-aaa8-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154856 Medicinska fakulteta Fakulteta za farmacijo 0 0 0