DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models
文献类型：期刊论文
| 作者 | Zhang, Zongwang1,3; Wu, Yanwei3; Wu, Bing2,3; Qi, Qing3; Li, Heng2,3; Lu, Huimin2,3; Fan, Chen3; Feng, Chunlan3; Zuo, Jianping2,3 ; Niu, Lili1
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| 刊名 | ARTHRITIS RESEARCH & THERAPY
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| 出版日期 | 2019-12-16 |
| 卷号 | 21期号:1页码:15 |
| ISSN号 | 1478-6354 |
| 关键词 | Systemic sclerosis SAHH inhibitor Fibrosis Inflammation Vasculopathy TGF-beta |
| DOI | 10.1186/s13075-019-2074-9 |
| 通讯作者 | Zuo, Jianping(jpzuo@simm.ac.cn) ; Niu, Lili(lilyniu@126.com) ; Tang, Wei(tangwei@simm.ac.cn) |
| 英文摘要 | Background: Systemic sclerosis is a multisystem inflammatory and vascular lesion leading to extensive tissue fibrosis. A reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, DZ2002, modulates the pathologic processes of various inflammatory diseases and autoimmune diseases. This study is designed to investigate the therapeutic potentiality of DZ2002 for experimental systemic sclerosis models. Methods: The anti-inflammatory and anti-fibrotic features of DZ2002 and its mechanisms were investigated in a bleomycin (BLM)-induced dermal fibrosis mice model. The effects of DZ2002 on expression of extracellular matrix components and TGF-beta signaling in human dermal fibroblasts were analyzed. Simultaneously, the effects of DZ2002 on macrophage activation and endothelial cell adhesion molecule expression were also evaluated. Results: DZ2002 significantly attenuated dermal fibrosis in BLM-induced mice. Consistently, DZ2002 inhibited the expression of various molecules associated with dermal fibrosis, including transforming growth factor beta 1, connective tissue growth factor, tumor necrosis factor-alpha, interferon-gamma, IL-1 beta, IL-4, IL-6, IL-10, IL-12p40, IL-17A, and monocyte chemotactic protein 1 in the lesional skin of BLM-induced mice. Furthermore, DZ2002 decreased the proportion of macrophages, neutrophils, and T cells (especially T helper cells) in the skin tissue of BLM-induced mice. In addition, DZ2002 attenuated both M1 macrophage and M2 macrophage differentiation in vivo and in vitro. Importantly, DZ2002 directly reversed the profibrotic phenotype of transforming growth factor-beta 1-treated dermal fibroblasts and suppressed ICAM-1, VCAM-1, VEGF, bFGF, and ET-1 expression in endothelial cells. Finally, our investigations showed that DZ2002 relieved systemic sclerosis by regulating fibrosis TGF-beta/Smad signaling pathway. Conclusions: DZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types and would be a potential drug for the treatment of systemic sclerosis. |
| WOS关键词 | INTERCELLULAR-ADHESION MOLECULE-1 ; REVERSIBLE SAHH INHIBITOR ; INCREASED EXPRESSION ; INTEGRIN ALPHA-V-BETA-5 ; S-ADENOSYLMETHIONINE ; CELLS ; TRANSMETHYLATION ; ESTABLISHMENT ; FIBROBLASTS ; CONTRIBUTES |
| 资助项目 | Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020113] ; Science & Technology Commission of Shanghai Municipality, China[18431907100] |
| WOS研究方向 | Rheumatology |
| 语种 | 英语 |
| 出版者 | BMC |
| WOS记录号 | WOS:000509121200004 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282390]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zuo, Jianping; Niu, Lili; Tang, Wei |
| 作者单位 | 1.Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 2004, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Zongwang,Wu, Yanwei,Wu, Bing,et al. DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models[J]. ARTHRITIS RESEARCH & THERAPY,2019,21(1):15. |
| APA | Zhang, Zongwang.,Wu, Yanwei.,Wu, Bing.,Qi, Qing.,Li, Heng.,...&Tang, Wei.(2019).DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models.ARTHRITIS RESEARCH & THERAPY,21(1),15. |
| MLA | Zhang, Zongwang,et al."DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models".ARTHRITIS RESEARCH & THERAPY 21.1(2019):15. |
入库方式： OAI收割
来源：上海药物研究所
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