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Ezrin regulates synovial angiogenesis in rheumatoid arthritis through YAP and Akt signalling
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- This study aimed to investigate the role and regulatory mechanisms of Ezrin in synovial vessels in rheumatoid arthritis (RA). Synovial tissues were obtained from people with osteoarthritis people and patients with RA patients. We also used an antigen‐induced arthritis (AIA) mice model by using Freund's adjuvant injections. Ezrin expression was analysed by immunofluorescence and immunohistochemical staining in synovial vessels of patients with RA and AIA mice. We investigated the role of Ezrin on vascular endothelial cells and its regulatory mechanism in vivo and in vitro by adenoviral transfection technology. Our results suggest a role for the Ezrin protein in proliferation, migration and angiogenesis of vascular endothelial cells in RA. We also demonstrate that Ezrin plays an important role in vascular endothelial cell migration and tube formation through regulation of the Hippo‐yes‐associated protein 1 (YAP) pathway. YAP, as a key protein, can further regulate the activity of PI3K/Akt signalling pathway in vascular endothelial cells. In AIA mice experiments, we observed that the inhibition of Ezrin or of its downstream YAP pathway can affect synovial angiogenesis and may lead to progression of RA. In conclusion, Ezrin plays an important role in angiogenesis in the RA synovium by regulating YAP nuclear translocation and interacting with the PI3K/Akt signalling pathway.
- Subjects :
- rheumatoid arthritis
Male
Angiogenesis
Gene Expression
Arthritis
Cell Cycle Proteins
Ezrin
macromolecular substances
Severity of Illness Index
Cell Line
Arthritis, Rheumatoid
angiogenesis
Mice
medicine
Animals
Humans
Cells, Cultured
PI3K/AKT/mTOR pathway
Aged
Aged, 80 and over
Tube formation
PI3K/Akt
Neovascularization, Pathologic
business.industry
Synovial Membrane
Original Articles
Hippo‐YAP
Cell Biology
Transfection
Middle Aged
medicine.disease
Immunohistochemistry
Endothelial stem cell
Cytoskeletal Proteins
Disease Models, Animal
Disease Progression
Cancer research
Molecular Medicine
Original Article
Female
Disease Susceptibility
business
Proto-Oncogene Proteins c-akt
Biomarkers
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....3ea36576516cd8e0e4733793055fb065