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Dysregulated expression of arterial microRNAs and their target gene networks in temporal arteries of treatment-naïve patients with giant cell arteritis
ID
Kuret, Tadeja
(
Avtor
),
ID
Lakota, Katja
(
Avtor
),
ID
Čučnik, Saša
(
Avtor
),
ID
Jurčić, Vesna
(
Avtor
),
ID
Distler, Oliver
(
Avtor
),
ID
Rotar, Žiga
(
Avtor
),
ID
Hočevar, Alojzija
(
Avtor
),
ID
Sodin-Šemrl, Snežna
(
Avtor
),
ID
Frank Bertoncelj, Mojca
(
Avtor
)
PDF - Predstavitvena datoteka,
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(1,68 MB)
MD5: 11AADE74B0B487AA71ADB13BCDAFECE8
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/1422-0067/22/12/6520
Galerija slik
Izvleček
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.
Jezik:
Angleški jezik
Ključne besede:
giant cell arteritis
,
microRNA
,
arterial remodelling
,
microRNA-target genes
,
toll-like receptor signaling
,
arterial ultrasound
,
vision disturbances
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
MF - Medicinska fakulteta
FFA - Fakulteta za farmacijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2021
Št. strani:
19 str.
Številčenje:
Vol. 22, iss. 12, art. 6520
PID:
20.500.12556/RUL-135649
UDK:
616-002
ISSN pri članku:
1422-0067
DOI:
10.3390/ijms22126520
COBISS.SI-ID:
67607811
Datum objave v RUL:
23.03.2022
Število ogledov:
1064
Število prenosov:
101
Metapodatki:
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Objavi na:
Gradivo je del revije
Naslov:
International journal of molecular sciences
Skrajšan naslov:
Int. j. mol. sci.
Založnik:
MDPI
ISSN:
1422-0067
COBISS.SI-ID:
2779162
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:
17.06.2021
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
velikanski celični arteritis
,
mikroRNA
,
preoblikovanje arterij
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P3-0314
Naslov:
Sistemske avtoimunske bolezni
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