Inhibition of GSK3β protects against collagen type II‐induced arthritis associated with a decrease in synovial leukocyte infiltration and inhibition of endoplasmic reticulum stress and autophagy biomarkers
| العنوان: | Inhibition of GSK3β protects against collagen type II‐induced arthritis associated with a decrease in synovial leukocyte infiltration and inhibition of endoplasmic reticulum stress and autophagy biomarkers |
|---|---|
| المؤلفون: | Sheren F. Younes, Maha Fahad Saja, Faten A. Alradini, Samaa S Kamar, Norah M Alzamil, Amal F Dawood, Bahjat Al-Ani |
| المصدر: | Clinical and Experimental Pharmacology and Physiology. 47:1393-1401 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, Arthritis, Andrology, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Physiology (medical), Autophagy, Leukocytes, medicine, Animals, Enzyme Inhibitors, Protein kinase B, PI3K/AKT/mTOR pathway, Pharmacology, Glycogen Synthase Kinase 3 beta, Chemistry, Endoplasmic reticulum, Synovial Membrane, Endoplasmic Reticulum Stress, medicine.disease, Arthritis, Experimental, Rats, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Synovial membrane, Infiltration (medical), Biomarkers |
| الوصف: | We sought to determine whether TDZD-8, the inhibitor of the glycogen synthase kinase-3β (GSK3β), can protect the synovial membrane of the knee joint against injuries induced by collagen type II immunization (CIA) possibly via the downregulation of synovial leukocyte infiltration, endoplasmic reticulum stress (ERS), and autophagy. The model group of rats (CIA) were immunized over a period of 3 weeks with collagen type II, whereas the treated group of rats (CIA + TDZD-8) were treated with TDZD-8 (1 mg/kg) for 21 days after the completion of the immunization regimen. All rats were then killed at week 6. Harvested synovial tissues were prepared for immunohistochemistry staining, and synovial homogenates were assayed for biomarkers of ERS, autophagy, apoptosis, and cell survival and proliferation. In addition, blood samples were assayed for biomarkers of arthritis. Synovial tissue images showed that CIA enhanced leukocyte recruitment as demonstrated by an increased CD45+ (leukocyte common antigen) immunostaining, which was markedly decreased by TDZD-8. TDZD-8 also significantly (P < .05) inhibited collagen-induced autophagy biomarkers Beclin-1 and LC3II, the ERS biomarkers GRP-78, IRE1-α, XBPIs, and eIF2a, and the survival protein Bcl-2. Whereas, the collagen-induced proliferative biomarkers Akt and mTOR were not inhibited by TDZD-8, and CIA inhibited the apoptotic proteins CHOP and cleaved caspase-3, which were augmented by TDZD-8. We further demonstrated a significant (P < .05) correlation between autoantibodies generated during the course of arthritis and biomarkers of ERS and autophagy. We conclude that TDZD-8 inhibits CIA and decreases synovial leukocyte infiltration, ERS, and autophagy, which is independent of Akt/mTOR signalling. |
| تدمد: | 1440-1681 0305-1870 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4bfaeddb2986ea825e78bfc1e24f8c7d https://doi.org/10.1111/1440-1681.13305 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....4bfaeddb2986ea825e78bfc1e24f8c7d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401681 03051870 |
|---|