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

J 2025

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

KULÍŠKOVÁ, Petra; Ondřej ZAPLETAL; Peter SLANINA; Julie ŠTÍCHOVÁ; Marcela VLKOVÁ et al.

Základní údaje

Originální název

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

Autoři

KULÍŠKOVÁ, Petra; Ondřej ZAPLETAL; Peter SLANINA; Julie ŠTÍCHOVÁ; Marcela VLKOVÁ; Jan BAROŠ; Petr NĚMEC; Jiří LITZMAN; Přemysl SOUČEK a Tomáš FREIBERGER

Vydání

Gene, Amsterdam, Elsevier, 2025, 0378-1119

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30102 Immunology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.400 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00142487

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

rheumatoid arthritis; bronchial asthma; PLAUR gene expression; monocytes; macrophages

Štítky

14110114, 14110116, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2026 08:59, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

MUNI/A/1566/2023, interní kód MU

Název: Patogeneze imunopatologických chorob

Investor: Masarykova univerzita, Patogeneze imunopatologických chorob

MUNI/A/1716/2024, interní kód MU

Název: Imunopatologické choroby - jejich etiologie, patogenza a diagnostika

Investor: Masarykova univerzita, Imunopatologické choroby - jejich etiologie, patogenza a diagnostika

NU21-05-00438, projekt VaV

Název: Úloha alternativních forem uPAR v rozvoji imunopatologických reakcí

Investor: Ministerstvo zdravotnictví ČR, Úloha alternativních forem uPAR v rozvoji imunopatologických reakcí, Podprogram 1 - standardní

Citovat

KULÍŠKOVÁ, Petra; Ondřej ZAPLETAL; Peter SLANINA; Julie ŠTÍCHOVÁ; Marcela VLKOVÁ; Jan BAROŠ; Petr NĚMEC; Jiří LITZMAN; Přemysl SOUČEK a Tomáš FREIBERGER. Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages. Gene. Amsterdam: Elsevier, 2025, roč. 972, November 2025, s. 1-10. ISSN 0378-1119. Dostupné z: https://doi.org/10.1016/j.gene.2025.149837.

@article{2531027,
   author = {Kulíšková, Petra and Zapletal, Ondřej and Slanina, Peter and Štíchová, Julie and Vlková, Marcela and Baroš, Jan and Němec, Petr and Litzman, Jiří and Souček, Přemysl and Freiberger, Tomáš},
   article_location = {Amsterdam},
   article_number = {November 2025},
   doi = {https://doi.org/10.1016/j.gene.2025.149837},
   keywords = {rheumatoid arthritis; bronchial asthma; PLAUR gene expression; monocytes; macrophages},
   language = {eng},
   issn = {0378-1119},
   journal = {Gene},
   title = {Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages},
   url = {https://www.sciencedirect.com/science/article/pii/S0378111925006262?via%3Dihub},
   volume = {972},
   year = {2025}
}

TY  - JOUR
ID  - 2531027
AU  - Kulíšková, Petra - Zapletal, Ondřej - Slanina, Peter - Štíchová, Julie - Vlková, Marcela - Baroš, Jan - Němec, Petr - Litzman, Jiří - Souček, Přemysl - Freiberger, Tomáš
PY  - 2025
TI  - Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages
JF  - Gene
VL  - 972
IS  - November 2025
SP  - 1-10
EP  - 1-10
PB  - Elsevier
SN  - 03781119
KW  - rheumatoid arthritis
KW  - bronchial asthma
KW  - PLAUR gene expression
KW  - monocytes
KW  - macrophages
UR  - https://www.sciencedirect.com/science/article/pii/S0378111925006262?via%3Dihub
N2  - 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.
ER  -

KULÍŠKOVÁ, Petra; Ondřej ZAPLETAL; Peter SLANINA; Julie ŠTÍCHOVÁ; Marcela VLKOVÁ; Jan BAROŠ; Petr NĚMEC; Jiří LITZMAN; Přemysl SOUČEK a Tomáš FREIBERGER. Rheumatoid arthritis and bronchial asthma are associated with changes in PLAUR gene expression in monocytes and macrophages. \textit{Gene}. Amsterdam: Elsevier, 2025, roč.~972, November 2025, s.~1-10. ISSN~0378-1119. Dostupné z: https://doi.org/10.1016/j.gene.2025.149837.

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