دورية أكاديمية
Acetazolamide ameliorates the severity of collagen-induced arthritis in rats: Involvement of inducing synovial apoptosis and inhibiting Wnt/β-catenin pathway.
| العنوان: | Acetazolamide ameliorates the severity of collagen-induced arthritis in rats: Involvement of inducing synovial apoptosis and inhibiting Wnt/β-catenin pathway. |
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| المؤلفون: | Mu YR; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, PR China., Cai L; Department of Pathology, School of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, PR China., Zhou MY; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, PR China., Liu MM; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, PR China., Li Z; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, PR China., Li R; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, PR China. Electronic address: aydlirong@163.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2021 Jan; Vol. 90, pp. 107214. Date of Electronic Publication: 2020 Dec 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Acetazolamide/*pharmacology , Antirheumatic Agents/*pharmacology , Apoptosis/*drug effects , Arthritis, Experimental/*drug therapy , Synovial Membrane/*drug effects , Wnt Signaling Pathway/*drug effects, Animals ; Apoptosis Regulatory Proteins/metabolism ; Aquaporin 1/antagonists & inhibitors ; Aquaporin 1/metabolism ; Arthritis, Experimental/chemically induced ; Arthritis, Experimental/metabolism ; Arthritis, Experimental/pathology ; Cell Proliferation/drug effects ; Cells, Cultured ; Collagen ; Disease Models, Animal ; Interleukin-1beta/metabolism ; Ki-67 Antigen/metabolism ; Male ; Rats, Sprague-Dawley ; Severity of Illness Index ; Synovial Membrane/metabolism ; Synovial Membrane/pathology ; Tumor Necrosis Factor-alpha/metabolism ; Rats |
| مستخلص: | We previously revealed that the overexpression of synovial aquaporin 1 (AQP1) aggravated collagen-induced arthritis (CIA) in rats via regulating β-catenin signaling. This study was to demonstrate the therapeutic effect of acetazolamide (AZ, an AQP1 inhibitor) on rat CIA and explored its underlying mechanisms. Paw swelling, arthritis index, pathological assessments, and serum levels of collagen type II (Col II) antibody, IL-1β and TNF-α were measured to evaluate the anti-arthritic effect of AZ on rat CIA. Ki67 immunohistochemistry and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of AZ on synovial cells in vivo. The protein levels of apoptosis-related genes and Wnt/β-catenin pathway key members were detected by western blot. We found that AZ treatment on CIA rats could inhibit paw swelling, reduce arthritis index, alleviate the pathologic changes of ankle joint and decrease the serum levels of Col II antibody, TNF-α and IL-1β. AZ could reduce Ki67 expression and increase apoptosis index in CIA synovial tissues by reducing Bcl-2 protein level, increasing Bax and caspase 3 protein levels and normalizing Bcl-2/Bax ratio. Moreover, AZ could reduce the protein levels of Wnt1, β-catenin, p-GSK-3β (Ser9), c-myc, cyclin D1 and MMP9, while increase GSK-3β protein level in CIA synovial tissues. Importantly, these mentioned effects of AZ (60 mg/kg) on CIA rats could be reversed by the combined use of lithium chloride (LiCl), an activator of Wnt/β-catenin pathway. In short, AZ exerted potent anti-arthritic effects on CIA rats by inducing synovial apoptosis and inhibiting Wnt/β-catenin pathway. (Copyright © 2020 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acetazolamide; Apoptosis; Aquaporin 1; Collagen-induced arthritis; Synoviocyte; Wnt/β-catenin pathway |
| المشرفين على المادة: | 0 (Antirheumatic Agents) 0 (Apoptosis Regulatory Proteins) 0 (Aqp1 protein, rat) 0 (IL1B protein, rat) 0 (Interleukin-1beta) 0 (Ki-67 Antigen) 0 (MKi67 protein, rat) 0 (Tumor Necrosis Factor-alpha) 146410-94-8 (Aquaporin 1) 9007-34-5 (Collagen) O3FX965V0I (Acetazolamide) |
| تواريخ الأحداث: | Date Created: 20201205 Date Completed: 20210607 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| DOI: | 10.1016/j.intimp.2020.107214 |
| PMID: | 33278748 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2020.107214 |