Department of Ophthalmology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2022 Jun 3;13:869519. doi: 10.3389/fendo.2022.869519. eCollection 2022.
Diabetic retinopathy (DR) is one of the most severe microvascular complications of diabetes mellitus (DM). Secreted protein acidic and rich in cysteine (SPARC) has been found to play an important role in many diseases, but its role and mechanism in DR remain unknown.
We studied the role of SPARC and integrin β1 in vascular pathophysiology and identified potential therapeutic translation. The SPARC levels were tested in human serum and vitreous by ELISA assay, and then the Gene Expression Omnibus (GEO) dataset was used to understand the key role of the target gene in DR. In human retinal capillary endothelial cells (HRCECs), we analyzed the mRNA and protein level by RT-PCR, immunohistochemistry, and Western blotting. The cell apoptosis, cell viability, and angiogenesis were analyzed by flow cytometry, CCK-8, and tube formation.
In this study, we investigated the role of SPARC in the development and progression of human DR and high glucose-induced HRCEC cells and found that the SPARC-ITGB1 signaling pathway mimics early molecular and advanced neurovascular pathophysiology complications of DR. The result revealed that DR patients have a high-level SPARC expression in serum and vitreous. Knockdown of SPARC could decrease the expressions of inflammatory factors and VEGFR, inhibit cell apoptosis and angiogenesis, and increase cell viability by regulating integrin β1 in HRCECs.
SPARC promotes diabetic retinopathy the regulation of integrin β1. The results of this study can provide a potential therapeutic application for the treatment of DR.
糖尿病视网膜病变（DR）是糖尿病（DM）最严重的微血管并发症之一。富含半胱氨酸的酸性分泌蛋白（SPARC）已被发现在许多疾病中发挥重要作用，但它在 DR 中的作用和机制尚不清楚。
我们研究了 SPARC 和整合素β1 在血管病理生理学中的作用，并确定了潜在的治疗转化。通过 ELISA 测定法检测人血清和玻璃体内的 SPARC 水平，然后使用基因表达综合数据库（GEO）数据集了解靶基因在 DR 中的关键作用。在人视网膜毛细血管内皮细胞（HRCEC）中，通过 RT-PCR、免疫组织化学和 Western blot 分析 mRNA 和蛋白水平。通过流式细胞术、CCK-8 和管形成分析细胞凋亡、细胞活力和血管生成。
在这项研究中，我们研究了 SPARC 在人类 DR 和高糖诱导的 HRCEC 细胞的发生和发展中的作用，发现 SPARC-ITGB1 信号通路模拟了 DR 的早期分子和晚期神经血管病理生理学并发症。结果表明，DR 患者血清和玻璃体内的 SPARC 表达水平较高。SPARC 敲低可通过调节 HRCEC 中的整合素β1 降低炎症因子和 VEGFR 的表达，抑制细胞凋亡和血管生成，增加细胞活力。
SPARC 促进糖尿病视网膜病变，其作用可能是通过调节整合素β1 实现的。本研究结果可为 DR 的治疗提供潜在的治疗应用。
