Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal neovascularization
Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal neovascularization
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人参皂苷Rh2抑制血管内皮生长因子诱导的角膜新生血管形成
DOI：
10.1096/fj.201701074rr
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Cao Cong
中科院分区：
文献类型：
--
作者：
Zhang Xiao-Pei;Li Ke-Ran;Yu Qing;Yao Mu-Di;Ge Hui-Min;Li Xiu-Miao;Jiang Qin;Yao Jin;Cao Cong
血管内皮生长因子诱导的新生血管在角膜新生血管形成中起着关键作用。本研究探讨了人参皂苷Rh2(GRh2)对新生血管的潜在作用。在体外培养的人脐静脉内皮细胞中，GRh2可显著抑制血管内皮生长因子诱导的细胞增殖、迁移和血管样管的形成，在分子水平上阻断血管内皮细胞中血管内皮生长因子受体2(VEGFR2)-GRB-2相关结合蛋白1(GAB1)的结合，导致AKT和ERK下游信号失活。GAB1基因敲除(通过靶向短发夹状RNA)类似地抑制HUVEC的增殖和迁移。值得注意的是，在GAB1沉默的HUVEC中，GRh2对血管内皮细胞生长因子的作用无效。在小鼠角膜碱烧伤模型中，GRh2滴眼液抑制了碱诱导的角膜新生血管和炎症细胞的渗透。此外，碱诱导的角膜中mRNAs/长非编码RNA的表达在很大程度上被GRh2减弱。总之，GRh2通过抑制VEGFR2-GAB1信号转导途径抑制了VEGF诱导的血管生成效应，也减轻了碱烧伤小鼠角膜的血管生成和炎症反应。FASE B J.32,3782-3791(2018)。Www.fasebj.org
VEGF‐induced neovascularization plays a pivotal role in corneal neovascularization (CoNV). The current study investigated the potential effect of ginsenoside Rh2 (GRh2) on neovascularization. In HUVECs, pretreatment with GRh2 largely attenuated VEGF‐induced cell proliferation, migration, and vessel‐like tube formationin vitro.At the molecular level, GRh2 disrupted VEGF‐induced VEGF receptor 2(VEGFR2)‐Grb‐2‐associated binder 1 (Gab1) association in HUVECs, causing inactivation of downstream AKT and ERK signaling. Gab1 knockdown (by targeted short hairpin RNA) similarly inhibited HUVEC proliferation and migration. Notably, GRh2 was ineffective against VEGF in Gab1‐silenced HUVECs. In a mouse cornea alkali burn model, GRh2 eyedrops inhibited alkali‐induced neovascularization and inflammatory cell infiltrations in the cornea. Furthermore, alkali‐induced corneal expression ofmRNAs/longnoncoding RNAs in cornea were largely attenuated by GRh2. Overall, GRh2 inhibits VEGF‐induced an‐giogenic effectviainhibiting VEGFR2‐Gab1 signaling invitro.It also alleviates angiogenic and inflammatory responses in alkali burn‐treated mouse corneas.—Zhang, X.‐P., Li, K.‐R., Yu, Q., Yao, M.‐D., Ge, H.‐M., Li, X.‐M., Jiang, Q., Yao, J., Cao, C. Ginsenoside Rh2 inhibits vascular endothelial growth factor‐induced corneal neovascularization. FASEB J. 32, 3782–3791 (2018). www.fasebj.org