The protein-protein interaction between connective tissue growth factor and annexin A2 is relevant to pannus formation in rheumatoid arthritis
| Autor: | Shengwei Jin, Xinxin Yu, Jianguang Wang, Wei Zhang, Qingqing Tian, Nannan Xu, Daoxing Chen, Guoyu Yin, Chenglin Yang, Lin Zhao, Gan Wu, Ben Cao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Angiogenesis
medicine.medical_treatment Connective tissue Diseases of the musculoskeletal system Arthritis Rheumatoid Mice Bimolecular fluorescence complementation Tandem Mass Spectrometry medicine Animals Humans Pannus Annexin A2 Tube formation integumentary system Chemistry Growth factor Connective Tissue Growth Factor Connective tissue growth factor (CTGF) Cell biology Molecular Docking Simulation CTGF HEK293 Cells medicine.anatomical_structure RC925-935 Pannus formation Rheumatoid arthritis (RA) Annexin A2 (ANXA2) Chromatography Liquid Research Article Binding domain |
| Zdroj: | Arthritis Research & Therapy, Vol 23, Iss 1, Pp 1-13 (2021) Arthritis Research & Therapy |
| ISSN: | 1478-6362 |
| Popis: | Background Connective 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. Methods CTGF-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. Results ANXA2 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. Conclusions TSP-1 is the essential domain in CTGF/ANXA2 interaction and contributes to FLS migration and pannus formation, inducing the process of RA. |
| Databáze: | OpenAIRE |
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