Tandem mass tag-based proteomic analysis reveals cathepsin-mediated anti-autophagic and pro-apoptotic effects under proliferative diabetic retinopathy.
Tandem mass tag-based proteomic analysis reveals cathepsin-mediated anti-autophagic and pro-apoptotic effects under proliferative diabetic retinopathy.
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DOI：
10.18632/aging.202217
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发表时间：
2020-12-03
期刊：
影响因子：
--
通讯作者：
Hu B
中科院分区：
文献类型：
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作者：
Niu R;Wang J;Geng C;Li Y;Dong L;Liu L;Chang Y;Shen J;Nie Z;Zhang Y;Hu B
糖尿病视网膜病变（PDR）是糖尿病的一种严重并发症，可导致失明。然而，现有的治疗方法对PDR的疗效并不令人满意，并产生不良反应，这是由于缺乏对该疾病的致病机制的理解。本研究采用串联质谱标记技术，结合液相色谱和串联质谱技术，对孔源性视网膜脱离和PDR患者玻璃体液中差异表达的蛋白质进行鉴定。数据可通过ProteomeXchange获得，标识符为PXD 021788。之后，在另一组的玻璃体和血清中证实了组织蛋白酶B、D和L的蛋白表达下调。在额外队列的血细胞中证实了3种组织蛋白酶的基因表达谱。此外，在高糖（HG）处理的视网膜血管内皮细胞培养物中重现组织蛋白酶表达模式，组织蛋白酶B或D下调介导了HG诱导的抗自噬和促凋亡作用，从而可能有助于高血糖下的血管病变。这项研究证明了以前未描述的组织蛋白酶的表达模式，揭示了一种新的组织蛋白酶参与的PDR下的致病机制，并揭示了这种衰弱性视网膜疾病的潜在治疗靶点。
Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes and can cause blindness. However, the available therapeutic modalities to PDR have unsatisfactory efficacies and incur adverse effects, which is due to the paucity in the understanding of pathogenic mechanisms responsible for the disease. In this study, tandem mass tag labeling technology combined with liquid chromatography and tandem mass spectrometry were utilized to identify differentially expressed proteins in vitreous humor of patients with rhegmatogenous retinal detachment and PDR. The data are available via ProteomeXchange with identifier PXD021788. Afterwards, the downregulated protein expression of Cathepsin B, D, and L was verified in vitreous and serum of another cohort. The gene expression profiling of the 3 cathepsins was confirmed in blood cells of an extra cohort. Furthermore, in high glucose (HG)-treated retinal vascular endothelial cell cultures recapitulating the cathepsin expression patterns, Cathepsin B or D downregulation mediated the HG-induced anti-autophagic and pro-apoptotic effects, thereby may contribute to vascular lesions under hyperglycemia. This study demonstrates previously undescribed expression patterns of cathepsins, reveals a novel cathepsin-involved pathogenic mechanism under PDR, and sheds light on potential therapeutic targets to this debilitating retinal disease.