ArticleArthritis research & therapy2021
The protein-protein interaction between connective tissue growth factor and annexin A2 is relevant to pannus formation in rheumatoid arthritis.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 15 citations in OpenAlex.
- Annexins and autoantibodies in autoimmune diseases - Insights into SLE, APS and RA: A review.Biomolecules & biomedicine · 2026Review
- Structural insights into regulation of CCN protein activities and functions.Journal of cell communication and signaling · 2023Review
- A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.BMC biotechnology · 2023Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Organokines in Rheumatoid Arthritis: A Critical Review.International journal of molecular sciences · 2022Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConnective tissue growth factor (CTGF)-induced angiogenesis is a crucial factor in rheumatoid arthritis (RA), but CTGF-interacting protein and related molecular mechanism of their interaction have not been fully elucidated.
methodsCTGF-interacting proteins were identified through the LC-MS/MS analysis of the Co-IP products from fibroblast-like synoviocyte (FLS) lysates, and the interaction between CTGF and annexin A2 (ANXA2) was further confirmed through Co-IP and BiFC assay. The binding domain, mutant, mechanism, and angiogenesis function were assessed by homology modeling, molecular docking, MTT, cell scratch, tube formation, and chick chorioallantoic membrane (CAM) assays. Additionally, severe combined immunodeficiency (SCID) mouse co-implantation model was constructed to confirm the effect of ANXA2/CTGF-TSP1 in the process of RA in vivo.
resultsANXA2 was identified and verified as an interaction partner of CTGF for the first time by Co-IP and LC-MS/MS analysis. Co-localization of CTGF and ANXA2 was observed in RA-FLS, and direct interaction of the TSP-1 domain of CTGF and ANXA2 was determined in HEK293T cells. The spatial conformation and stable combination of the ANXA2/CTGF-TSP1 complex were assessed by homology modeling in the biomimetic environment. The function of the ANXA2/CTGF-TSP1 complex was proved on promoting FLS proliferation, migration, and angiogenesis in vitro and deteriorating FLS invasion and joint damage in SCID mice.
conclusionsTSP-1 is the essential domain in CTGF/ANXA2 interaction and contributes to FLS migration and pannus formation, inducing the process of RA.
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