دورية أكاديمية
Development of a novel Poly (I:C)-induced murine model with accelerated lupus nephritis and examination of the therapeutic effects of mycophenolate mofetil and a cathepsin S inhibitor.
| العنوان: | Development of a novel Poly (I:C)-induced murine model with accelerated lupus nephritis and examination of the therapeutic effects of mycophenolate mofetil and a cathepsin S inhibitor. |
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| المؤلفون: | Kawato Y; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan. Electronic address: yuka.kawato@astellas.com., Fukahori H; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan., Nakamura K; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan., Kubo K; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan., Hiramitsu M; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan., Kinugasa F; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan., Morokata T; Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan. |
| المصدر: | European journal of pharmacology [Eur J Pharmacol] 2023 Jan 05; Vol. 938, pp. 175440. Date of Electronic Publication: 2022 Dec 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : Amsterdam : Elsevier Science Original Publication: Amsterdam, North Holland Pub. Co. |
| مواضيع طبية MeSH: | Lupus Nephritis*/chemically induced , Lupus Nephritis*/drug therapy , Lupus Erythematosus, Systemic*/drug therapy, Mice ; Animals ; Mycophenolic Acid/pharmacology ; Mycophenolic Acid/therapeutic use ; Disease Models, Animal ; Poly I-C/pharmacology ; Mice, Inbred NZB ; Immunosuppressive Agents/pharmacology ; Immunosuppressive Agents/therapeutic use |
| مستخلص: | Systemic lupus erythematosus (SLE) is an autoimmune disease involving multi-organ systems with a widely heterogeneous clinical presentation. Renal involvement, observed mainly in lupus nephritis (LN), is the most common organ lesion associated with SLE and a determinant of prognosis. However, treatment of LN remains controversial and challenging, prompting the need for novel therapeutic approaches. In particular, development of a clinically relevant LN animal model would greatly facilitate the development of new treatments. Here, we report a novel murine model for LN established by administering polyinosinic-polycytidylic acid (Poly (I:C)) to NZB/W F1 mice. We investigated the effectiveness of administering Poly (I:C) to NZB/W F1 mice for accelerating nephritis onset and explored the optimal conditions under which to enroll mice with nephritis with similar pathology for studying treatment candidates. Gene-expression analysis revealed that activation of macrophages, which are reported to be involved in the progression of LN in patients, was a unique characteristic in this accelerated nephritis model. Evaluation of the therapeutic effect of mycophenolate mofetil (MMF), a recommended first-choice agent for LN, in this novel LN model showed that MMF significantly reduced proteinuria. The cathepsin S (CatS) inhibitor ASP1617, which has been reported to prevent development of lupus-like glomerulonephritis in the spontaneous NZB/W F1 mouse model, also showed marked therapeutic effect in this model. Our novel Poly (I:C) accelerated LN model would thus be very useful for screening clinical candidates for LN, and CatS may be an attractive therapeutic target for the treatment of LN. Competing Interests: Declaration of competing interest All authors are employees of Astellas Pharma, who provided funding for this study. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Cathepsin S; Lupus nephritis; Mycophenolate mofetil; NZB/W F1 mice; Polyinosinic-polycytidylic acid |
| المشرفين على المادة: | HU9DX48N0T (Mycophenolic Acid) EC 3.4.22.27 (cathepsin S) O84C90HH2L (Poly I-C) 0 (Immunosuppressive Agents) |
| تواريخ الأحداث: | Date Created: 20221204 Date Completed: 20221219 Latest Revision: 20221221 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.ejphar.2022.175440 |
| PMID: | 36463947 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0712 |
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| DOI: | 10.1016/j.ejphar.2022.175440 |