Salubrinal attenuated retinal neovascularization by inhibiting CHOP-HIF1α-VEGF pathways.
Salubrinal attenuated retinal neovascularization by inhibiting CHOP-HIF1α-VEGF pathways.
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Salubrinal 通过抑制 CHOP-HIF1 α-VEGF 途径减弱视网膜新生血管形成
DOI：
10.18632/oncotarget.20431
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发表时间：
2017-09-29
期刊：
影响因子：
--
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Hu Y;Lu X;Xu Y;Lu L;Yu S;Cheng Q;Yang B;Tsui CK;Ye D;Huang J;Liang X
视网膜新生血管（RNV）相关疾病是世界上不可逆失明的主要原因。本研究的目的是确定 salubrinal 是否可以通过抑制小鼠视网膜微血管内皮细胞 (mRMEC) 和氧诱导性视网膜病变中的 CCAAT/增强子结合蛋白 (C/EBP) 同源蛋白 (CHOP)-缺氧诱导因子 1α (HIF1α)-血管内皮生长因子 (VEGF) 通路来减弱 RNV （OIR）小鼠模型。经过salubrinal (20μmol/L)或CHOP-siRNA处理后，mRMECs暴露于缺氧环境。 OIR小鼠从P12到P17腹腔注射salubrinal（0.5mg/kg/天）。通过 salubrinal 或 CHOP-siRNA 治疗，缺氧诱导的 mRMEC 中升高的 CHOP 蛋白和 mRNA 水平显着降低。缺氧条件下HIF1α-VEGF通路被激活，经过salubrinal或CHOP-siRNA处理后，HIF1α蛋白被降解，VEGF分泌下调。在 OIR 小鼠中，Salubrinal 治疗后 RNV 面积显着减少。此外，OIR小鼠视网膜中升高的CHOP、HIF1α和VEGF表达在salubrinal治疗后均有所降低。这表明 salubrinal 通过抑制 CHOP-HIF1α-VEGF 通路来减弱 mRMEC 和 OIR 小鼠的 RNV，并且可能成为缺氧诱导的视网膜微血管病的潜在治疗靶点。
Retinal neovascularization (RNV) related disease is the leading cause of irreversible blindness in the world. The aim of this study is to identify whether salubrinal could attenuate RNV by inhibiting CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP)- hypoxia inducible factors 1α (HIF1α) -vascular endothelial growth factor (VEGF) pathways in both mouse retinal microvascular endothelial cells (mRMECs) and oxygen-induced retinopathy (OIR) mouse model. After being treated with salubrinal (20μmol/L) or CHOP-siRNA, mRMECs were exposed to a hypoxia environment. OIR mice were intraperitoneally injected with salubrinal (0.5 mg/kg/day) from P12 to P17. With salubrinal or CHOP-siRNA treatment, the elevated CHOP protein and mRNA levels in hypoxia-induced mRMECs were significantly decreased. HIF1α-VEGF pathways were activated under hypoxia condition, then HIF1α protein was degraded and VEGF secretion was down-regulated after salubrinal or CHOP-siRNA treatment. In OIR mice, the areas of RNV were markedly decreased with salubrinal treatment. Moreover, elevated expressions of CHOP, HIF1α and VEGF in retinas of OIR mice were all reduced after salubrinal treatment. It suggested that salubrinal attenuated RNV in mRMECs and OIR mice by inhibiting CHOP-HIF1α-VEGF pathways and could be a potential therapeutic target for hypoxia-induced retinal microangiopathy.
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影响因子：
4
作者：
He, Yun-Yun;Liu, Chun-Lei;He, Kun-Lun
通讯作者：
He, Kun-Lun
影响因子：
5.8
作者：
Mazure, NM;Brahimi-Horn, MC;Pouysségur, J
通讯作者：
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影响因子：
6.1
作者：
Anuncibay-Soto B;Santos-Galdiano M;Fernández-López A
通讯作者：
Fernández-López A
影响因子：
3.4
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Pallet, Nicolas