Dysregulated expression of arterial microRNAs and their target gene networks in temporal arteries of treatment-naïve patients with giant cell arteritis

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

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.

• Language: English
• Keywords: giant cell arteritis, microRNA, arterial remodelling, microRNA-target genes, toll-like receptor signaling, arterial ultrasound, vision disturbances
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 19 str.
• Numbering: Vol. 22, iss. 12, art. 6520
• PID: 20.500.12556/RUL-135649
• UDC: 616-002
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms22126520
• COBISS.SI-ID: 67607811
• Publication date in RUL: 23.03.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 17.06.2021

Secondary language

• Language: Slovenian
• Keywords: velikanski celični arteritis, mikroRNA, preoblikovanje arterij

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0314
• Name: Sistemske avtoimunske bolezni