Idioma:

Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts

Tsoyi, Konstantin ; Esposito, Anthony J ; Sun, Bo ; Bowen, Ryan G ; Xiong, Kevin ; Poli, Fernando ; Cardenas, Rafael ; Chu, Sarah G ; Liang, Xiaoliang ; Ryter, Stefan W ; Beeton, Christine ; Doyle, Tracy J ; Robertson, Matthew J ; Celada, Lindsay J ; Romero, Freddy ; El-Chemaly, Souheil Y ; Perrella, Mark A ; Ho, I-Cheng ; Rosas, Ivan O

Scientific reports, 2022-02, Vol.12 (1), p.2847-11, Article 2847 [Periódico revisado por pares]

England: Nature Publishing Group

Texto completo disponível

Citações Citado por

Enviar para

Título:
Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts
Autor: Tsoyi, Konstantin ; Esposito, Anthony J ; Sun, Bo ; Bowen, Ryan G ; Xiong, Kevin ; Poli, Fernando ; Cardenas, Rafael ; Chu, Sarah G ; Liang, Xiaoliang ; Ryter, Stefan W ; Beeton, Christine ; Doyle, Tracy J ; Robertson, Matthew J ; Celada, Lindsay J ; Romero, Freddy ; El-Chemaly, Souheil Y ; Perrella, Mark A ; Ho, I-Cheng ; Rosas, Ivan O
Assuntos: AKT protein ; Animals ; Anti-Citrullinated Protein Antibodies - genetics ; Arthritis ; Arthritis, Rheumatoid - complications ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - genetics ; Arthritis, Rheumatoid - pathology ; Bleomycin ; Bleomycin - toxicity ; Citrullination - genetics ; Citrulline ; Extracellular matrix ; Fibroblasts ; Fibroblasts - metabolism ; Fibrosis ; Gene expression ; Gene Expression Regulation - genetics ; Humans ; Inflammation ; Kinases ; Lung - metabolism ; Lung - pathology ; Lung diseases ; Lung Injury - chemically induced ; Lung Injury - complications ; Lung Injury - genetics ; Lung Injury - pathology ; Mice ; Mice, Transgenic ; Morbidity ; Phosphatidylinositol 3-Kinases - genetics ; Protein-arginine deiminase ; Protein-Arginine Deiminase Type 2 - genetics ; Proteins ; Proteoglycans ; Proto-Oncogene Proteins c-akt - genetics ; Pulmonary Fibrosis - complications ; Pulmonary Fibrosis - drug therapy ; Pulmonary Fibrosis - genetics ; Pulmonary Fibrosis - pathology ; Receptor-Like Protein Tyrosine Phosphatases, Class 3 ; Rheumatoid arthritis ; Sp1 protein ; Sp1 Transcription Factor - genetics ; Syndecan ; Syndecan-2 - genetics ; Therapeutic targets ; Transgenic mice
É parte de: Scientific reports, 2022-02, Vol.12 (1), p.2847-11, Article 2847
Descrição: Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression of both RA and fibrotic lung disease; however, the role of protein citrullination in RA-ILD remains unclear. Here, we demonstrate that the expression of peptidylarginine deiminase 2 (PAD2), an enzyme that catalyzes protein citrullination, is increased in lung homogenates from subjects with RA-ILD and their lung fibroblasts. Chemical inhibition or genetic knockdown of PAD2 in RA-ILD fibroblasts attenuated their activation, marked by decreased myofibroblast differentiation, gel contraction, and extracellular matrix gene expression. Treatment of RA-ILD fibroblasts with the proteoglycan syndecan-2 (SDC2) yielded similar antifibrotic effects through regulation of PAD2 expression, phosphoinositide 3-kinase/Akt signaling, and Sp1 activation in a CD148-dependent manner. Furthermore, SDC2-transgenic mice exposed to bleomycin-induced lung injury in an inflammatory arthritis model expressed lower levels of PAD2 and were protected from the development of pulmonary fibrosis. Together, our results support a SDC2-sensitive profibrotic role for PAD2 in RA-ILD fibroblasts and identify PAD2 as a promising therapeutic target of RA-ILD.
Editor: England: Nature Publishing Group
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts

England: Nature Publishing Group

Buscando em bases de dados remotas. Favor aguardar.