| http://purl.uniprot.org/citations/35181688 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35181688 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41598-022-06678-7"xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Liang X."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Sun B."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Xiong K."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Robertson M.J."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Perrella M.A."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Romero F."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Rosas I.O."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Poli F."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Ho I.C."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Beeton C."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Doyle T.J."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Cardenas R."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Ryter S.W."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Tsoyi K."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Chu S.G."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Esposito A.J."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Celada L.J."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "Bowen R.G."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/author | "El-Chemaly S.Y."xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
| http://purl.uniprot.org/citations/35181688 | http://purl.uniprot.org/core/pages | "2847"xsd:string |