ArticleScientific reports2022
Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Molecular Systems Architecture of Fibrotic Lung Microenvironment in Idiopathic Pulmonary Fibrosis.Cells · 2026Pooled it
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Molecular insights into the anti-inflammatory and antifibrotic effects of licorice-ginger decoction in experimental models of inflammatory arthritis-associated lung fibrosis.Immunology and cell biology · 2026Article
- Regulation of basal and tumour necrosis factor α-induced fibroblast gene expression by peptidylarginine deiminase 2.The Journal of physiology · 2026Article
- Review
- Fibrinogen triggers perivascular fibroblast activation in a mouse model of cortical ischemic stroke.iScience · 2025Article
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- AMF30a promotes survival and function of human corneal endothelial cells by regulating TGF-β/ROCK/HIPPO pathway.Scientific reports · 2025Article
- Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts.Biochemical and biophysical research communications · 2025Article
- Macrophage subtypes and pathways in autoimmune interstitial lung diseases: potential therapeutic targets.Frontiers in immunology · 2025Article
- Shared immunological pathways in rheumatoid arthritis-related interstitial lung disease.Frontiers in immunology · 2025Review
- PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation.PloS one · 2024Article
- Citrullination of matrisomal proteins in health and diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Etiology and Pathogenesis of Rheumatoid Arthritis-Interstitial Lung Disease.International journal of molecular sciences · 2023Review
- The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
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