Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai, China.
Ophthalmic Res. 2020;63(2):122-132. doi: 10.1159/000503637. Epub 2020 Jan 21.
We characterized the role of aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) in retinal inflammation and apoptosis regulation, both in vivo and in vitro. In addition, we used clinical specimens to show the relationship between AIMP1 and the development of diabetic retinopathy (DR).
To elucidate the role of AIMP1 in DR.
A diabetic AIMP1-specific knockout (KO) C57 mouse model was used. Human retinal microvascular endothelial cells (HRMECs) were incubated with normal glucose, high glucose (HG), and HG + AIMP1-small interfering RNA (siRNA). The expression of AIMP1 and relative inflammatory and apoptotic cytokines in diabetic mice retina and HRMECs were measured using Western blotting and polymerase chain reaction. The apoptosis of HRMECs was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The levels of AIMP1 in the vitreous humor and serum were determined using ELISA. Possible correlations between the intravitreal level of AIMP1 and blood glucose, glycosylated hemoglobin HbA1c, intravitreal levels of IL-1β, and caspase-3 were determined.
The expression of inflammatory and apoptotic proteins was inhibited in the AIMP1 KO mice and HRMECs incubated with AIMP1-siRNA. The apoptosis of HRMECs was decreased in the AIMP1-siRNA group. The intravitreal level of AIMP1 in DR patients was significantly higher than that in nondiabetic patients (p < 0.01). There was a positive correlation between intravitreal AIMP1 and HbA1c and intravitreal IL-1β and caspase-3 (p < 0.05).
HG induced increased expression of AIMP1 in HRMECs and retinas from diabetic C57 mice, thereby increasing the expression of inflammatory and apoptotic cytokines, which promoted DR progression. A decrease in AIMP1 expression prevented the development of DR by inhibiting the activation of inflammatory and apoptotic signaling. Therefore, AIMP1 is an effective interfering target for the prevention and treatment of DR.
我们研究了氨酰-tRNA 合成酶相互作用多功能蛋白 1（AIMP1）在体内和体外调节视网膜炎症和细胞凋亡中的作用。此外，我们使用临床标本显示了 AIMP1 与糖尿病性视网膜病变（DR）发展之间的关系。
阐明 AIMP1 在 DR 中的作用。
使用糖尿病 AIMP1 特异性敲除（KO）C57 小鼠模型。将人视网膜微血管内皮细胞（HRMEC）在正常葡萄糖、高葡萄糖（HG）和 HG+AIMP1 小干扰 RNA（siRNA）中孵育。通过 Western blot 和聚合酶链反应测量糖尿病小鼠视网膜和 HRMEC 中 AIMP1 和相关炎症及凋亡细胞因子的表达。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记法检测 HRMEC 凋亡。通过 ELISA 测定玻璃体液和血清中 AIMP1 的水平。确定玻璃体内 AIMP1 水平与血糖、糖化血红蛋白 HbA1c、玻璃体内 IL-1β 和 caspase-3 之间的可能相关性。
在 AIMP1 KO 小鼠和用 AIMP1-siRNA 孵育的 HRMEC 中，炎症和凋亡蛋白的表达受到抑制。AIMP1-siRNA 组 HRMEC 凋亡减少。DR 患者玻璃体内 AIMP1 水平明显高于非糖尿病患者（p<0.01）。玻璃体内 AIMP1 与 HbA1c 和玻璃体内 IL-1β 和 caspase-3 呈正相关（p<0.05）。
HG 诱导 HRMEC 和糖尿病 C57 小鼠视网膜中 AIMP1 的表达增加，从而增加炎症和凋亡细胞因子的表达，促进 DR 的进展。降低 AIMP1 的表达通过抑制炎症和凋亡信号的激活来防止 DR 的发生。因此，AIMP1 是预防和治疗 DR 的有效干预靶点。
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