Nanomedicine & Vision Group, Facultad de Ciencias Biomédicas, Instituto de Investigaciones en Medicina Traslacional, Universidad Austral, Consejo Nacional de Investigaciones en Ciencia y Tecnología (CONICET), Pilar, Buenos Aires, Argentina.
Department of Ophthalmology, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina.
PLoS One. 2020 Feb 7;15(2):e0228895. doi: 10.1371/journal.pone.0228895. eCollection 2020.
Alpha-1-antitrypsin is a protein involved in avoidance of different processes that are seen in diabetic retinopathy pathogenesis. These processes include apoptosis, extracellular matrix remodeling and damage of vessel walls and capillaries. Furthermore, because of its anti-inflammatory effects, alpha-1-antitrypsin has been proposed as a possible therapeutic approach for diabetic retinopathy. Our group tested alpha-1-antitrypsin in a type 1 diabetes mouse model and observed a reduction of inflammation and retinal neurodegeneration. Thus, shedding light on the mechanism of action of alpha-1-antitrypsin at molecular level may explain how it works in the diabetic retinopathy context and show its potential for use in other retinal diseases.
In this work, we evaluated alpha-1-antitrypsin in an ARPE-19 human cell line exposed to high glucose. We explored the expression of different mediators on signaling pathways related to pro-inflammatory cytokines production, glucose metabolism, epithelial-mesenchymal transition and other proteins involved in the normal function of retinal pigment epithelium by RT-qPCR and Western Blot.
We obtained different expression patterns for evaluated mediators altered with high glucose exposure and corrected with the use of alpha-1-antitrypsin.
The expression profile obtained in vitro for the evaluated proteins and mRNA allowed us to explain our previous results obtained on mouse models and to hypothesize how alpha-1-antitrypsin hinder diabetic retinopathy progression on a complex network between different signaling pathways.
This network helps to understand the way alpha-1-antitrypsin works in diabetic retinopathy and its scope of action.
α-1 抗胰蛋白酶是一种参与避免糖尿病视网膜病变发病机制中多种过程的蛋白质。这些过程包括细胞凋亡、细胞外基质重塑以及血管壁和毛细血管的损伤。此外，由于其抗炎作用，α-1 抗胰蛋白酶已被提议作为治疗糖尿病性视网膜病变的一种可能方法。我们的研究小组在 1 型糖尿病小鼠模型中测试了α-1 抗胰蛋白酶，观察到炎症和视网膜神经退行性变减少。因此，阐明α-1 抗胰蛋白酶在分子水平上的作用机制可以解释其在糖尿病性视网膜病变中的作用方式，并展示其在其他视网膜疾病中的应用潜力。
在这项工作中，我们在暴露于高葡萄糖的 ARPE-19 人细胞系中评估了α-1 抗胰蛋白酶。我们通过 RT-qPCR 和 Western Blot 探索了与促炎细胞因子产生、葡萄糖代谢、上皮-间充质转化和视网膜色素上皮正常功能相关的信号通路中不同介质的表达。
我们获得了不同的表达模式，评估的介质在高葡萄糖暴露下发生改变，并通过使用α-1 抗胰蛋白酶得到纠正。
在体外评估的蛋白质和 mRNA 的表达谱使我们能够解释我们在小鼠模型中获得的先前结果，并假设α-1 抗胰蛋白酶如何在不同信号通路之间的复杂网络中阻止糖尿病视网膜病变的进展。
该网络有助于理解α-1 抗胰蛋白酶在糖尿病性视网膜病变中的作用方式及其作用范围。
