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Article

Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis

1
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
2
Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
3
Faculty of Mathematics, Natural Sciences and Information Technology, University of Primorska, 6000 Koper, Slovenia
4
Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
5
Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
6
Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
7
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Paul Quax
Int. J. Mol. Sci. 2021, 22(12), 6520; https://doi.org/10.3390/ijms22126520
Received: 29 April 2021 / Revised: 4 June 2021 / Accepted: 14 June 2021 / Published: 17 June 2021
(This article belongs to the Special Issue Molecular Research in Cardiovascular Disease)
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. View Full-Text
Keywords: giant cell arteritis; microRNA; microRNA-target genes; arterial remodelling; toll-like receptor signaling; arterial ultrasound; vision disturbances giant cell arteritis; microRNA; microRNA-target genes; arterial remodelling; toll-like receptor signaling; arterial ultrasound; vision disturbances
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MDPI and ACS Style

Kuret, T.; Lakota, K.; Čučnik, S.; Jurčič, V.; Distler, O.; Rotar, Ž.; Hočevar, A.; Sodin-Šemrl, S.; Frank-Bertoncelj, M. Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis. Int. J. Mol. Sci. 2021, 22, 6520. https://doi.org/10.3390/ijms22126520

AMA Style

Kuret T, Lakota K, Čučnik S, Jurčič V, Distler O, Rotar Ž, Hočevar A, Sodin-Šemrl S, Frank-Bertoncelj M. Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis. International Journal of Molecular Sciences. 2021; 22(12):6520. https://doi.org/10.3390/ijms22126520

Chicago/Turabian Style

Kuret, Tadeja, Katja Lakota, Saša Čučnik, Vesna Jurčič, Oliver Distler, Žiga Rotar, Alojzija Hočevar, Snežna Sodin-Šemrl, and Mojca Frank-Bertoncelj. 2021. "Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis" International Journal of Molecular Sciences 22, no. 12: 6520. https://doi.org/10.3390/ijms22126520

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