Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082236" target="_blank" >RIV/00159816:_____/25:00082236 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00142487

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378111925006262?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378111925006262?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gene.2025.149837" target="_blank" >10.1016/j.gene.2025.149837</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages

Popis výsledku v původním jazyce

The plasminogen activation system plays an important role in the pathogenesis of both rheumatoid arthritis (RA) and bronchial asthma (BA). Elevated levels of system components, including the urokinase plasminogen activator receptor (uPAR), have been observed in these conditions. The PLAUR gene, encoding uPAR, undergoes alternative splicing due to the presence of cassette exons, producing two major isoforms: membrane-bound uPAR (muPAR) and soluble uPAR (suPAR), distinguished by their membrane association determined by terminal exon usage. Given the increased suPAR levels reported in the plasma of RA and BA patients, we hypothesized that altered PLAUR expression, beyond post-translational muPAR cleavage, could contribute to disease susceptibility and progression. To test this, we analyzed PLAUR transcript levels and alternative splicing patterns in monocytes and macrophages (M0 and M1 phenotypes) isolated from 37 healthy volunteers and patients with RA (29 in total) and BA (31 in total), stratified by disease severity. Quantitative RT-PCR analysis revealed significantly elevated PLAUR expression in monocytes and M0 macrophages from both RA and BA patients compared to healthy controls. In mild BA, this increase was limited to overall expression, while severe BA was additionally characterized by an enrichment of low-abundance splicing isoforms: suPAR lacking exon 6 and muPAR lacking exon 5. These findings suggest that both increased PLAUR expression and alternative splicing events may contribute to the immunopathology of RA and BA. The relative abundance of suPAR isoforms may serve as a potential biomarker for disease progression, though further functional validation is necessary to elucidate their clinical relevance.

Název v anglickém jazyce

Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages

Popis výsledku anglicky

The plasminogen activation system plays an important role in the pathogenesis of both rheumatoid arthritis (RA) and bronchial asthma (BA). Elevated levels of system components, including the urokinase plasminogen activator receptor (uPAR), have been observed in these conditions. The PLAUR gene, encoding uPAR, undergoes alternative splicing due to the presence of cassette exons, producing two major isoforms: membrane-bound uPAR (muPAR) and soluble uPAR (suPAR), distinguished by their membrane association determined by terminal exon usage. Given the increased suPAR levels reported in the plasma of RA and BA patients, we hypothesized that altered PLAUR expression, beyond post-translational muPAR cleavage, could contribute to disease susceptibility and progression. To test this, we analyzed PLAUR transcript levels and alternative splicing patterns in monocytes and macrophages (M0 and M1 phenotypes) isolated from 37 healthy volunteers and patients with RA (29 in total) and BA (31 in total), stratified by disease severity. Quantitative RT-PCR analysis revealed significantly elevated PLAUR expression in monocytes and M0 macrophages from both RA and BA patients compared to healthy controls. In mild BA, this increase was limited to overall expression, while severe BA was additionally characterized by an enrichment of low-abundance splicing isoforms: suPAR lacking exon 6 and muPAR lacking exon 5. These findings suggest that both increased PLAUR expression and alternative splicing events may contribute to the immunopathology of RA and BA. The relative abundance of suPAR isoforms may serve as a potential biomarker for disease progression, though further functional validation is necessary to elucidate their clinical relevance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30225 - Allergy

Projekt

<a href="/cs/project/NU21-05-00438" target="_blank" >NU21-05-00438: Úloha alternativních forem uPAR v rozvoji imunopatologických reakcí</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Gene

ISSN

0378-1119

e-ISSN

1879-0038

Svazek periodika

972

Číslo periodika v rámci svazku

Nov 2025

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

149837

Kód UT WoS článku

001603887400001

EID výsledku v databázi Scopus

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