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DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3KAkt-NF-kappa B pathway

文献类型：期刊论文

作者Wu, Chun-mei1,2; Mao, Jia-wen3; Zhu, Jin-zhi4; Xie, Can-can1,5; Yao, Jia-ying6,7; Yang, Xiao-qian1; Xiang, Mai1,2; He, Yi-fan1,2; Tong, Xiao1,2; Litifu, Dilinaer1,2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2023-08-21
页码14
ISSN号1671-4083
关键词dry eye disease DZ2002 corneal angiogenesis immunomodulatory function NF-kappa B ophthalmic therapy
DOI10.1038/s41401-023-01146-y
通讯作者He, Shi-jun(heshijun@shutcm.edu.cn) ; Lin, Ze-min(linzemin@simm.ac.cn) ; Zuo, Jian-ping(jpzuo@simm.ac.cn)
英文摘要Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 mu L per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-kappa B pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-kappa B pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-kappa B pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.
WOS关键词REVERSIBLE SAHH INHIBITOR ; IN-VITRO ; VEGF ; LYMPHANGIOGENESIS ; EXPRESSION ; TNF
资助项目National Natural Science Foundation of China[81871240] ; Shanghai Municipal Science and Technology Major Project ; CAS Light of West China Program and CAS Interdisciplinary Innovation Team
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:001052530000001
源URL[http://119.78.100.183/handle/2S10ELR8/307046]  
专题新药研究国家重点实验室
通讯作者He, Shi-jun; Lin, Ze-min; Zuo, Jian-ping
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
4.Shanghai Xuhui Cent Hosp, Dept Pharm, Shanghai 200031, Peoples R China
5.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China
6.Jiangxi Univ Tradit Chinese Med, Coll Pharm, Nanchang 330004, Peoples R China
7.Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Chun-mei,Mao, Jia-wen,Zhu, Jin-zhi,et al. DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3KAkt-NF-kappa B pathway[J]. ACTA PHARMACOLOGICA SINICA,2023:14.
APA Wu, Chun-mei.,Mao, Jia-wen.,Zhu, Jin-zhi.,Xie, Can-can.,Yao, Jia-ying.,...&Zuo, Jian-ping.(2023).DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3KAkt-NF-kappa B pathway.ACTA PHARMACOLOGICA SINICA,14.
MLA Wu, Chun-mei,et al."DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3KAkt-NF-kappa B pathway".ACTA PHARMACOLOGICA SINICA (2023):14.

入库方式： OAI收割

来源：上海药物研究所

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