Xu Zepeng, Tian Ni, Li Songtao, Li Kunmeng, Guo Haike, Zhang Hongyang, Jin Haiying, An Meixia, Yu Xiaoyi
Department of Ophthalmology, Jiangmen Wuyi Hospital of TCM, Jiangmen 529000, Guangdong, China; The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China.
Department of Ophthalmology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510504, Guangdong, China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108234. doi: 10.1016/j.intimp.2021.108234. Epub 2021 Oct 13.
Diabetic retinopathy (DR) is a major cause of visual deficits and blindness in the working-age population and inflammatory response is a key event during DR. In this study, we investigated the anti-inflammatory properties of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in a diabetic rat model and human retinal microvascular endothelial cells. After development of DR in rats subjected to diabetes induction with streptozotocin (STZ), the DR rats were treated with different concentrations of hUCMSC-sEVs. Our results showed that the treatment of the retinas of DR rats with hUCMSC-sEVs not only reduced the level of vascular leakage in the retinas of rats but also decreased the retinal thickness as well as the associated inflammation. Further, our in vitro evidences suggest that hUCMSC-sEVs repress high glucose (HG)-induced cell inflammation and apoptosis. Subsequently, we analyzed the differentially expressed microRNAs (miRNAs) in the hUCMSC-sEVs by microarray and performed in silico studies to predict the target mRNA of miR-18b. Our findings also revealed that the expression of miR-18b was significantly elevated in the retina of diabetic rats after sEV treatment. In addition, miR-18b was found to target mitogen-activated protein kinase kinase kinase 1 (MAP3K1), thereby inhibiting NF-κB p65 phosphorylation to alleviate DR. Overall, this study highlights the potential of hUCMSCs-sEVs as biomaterials for anti-inflammatory and anti-apoptotic effects in DR by transferring miR-18b.
糖尿病视网膜病变（DR）是劳动年龄人群视力缺陷和失明的主要原因，炎症反应是DR过程中的关键事件。在本研究中，我们在糖尿病大鼠模型和人视网膜微血管内皮细胞中研究了源自人脐带间充质干细胞（hUCMSCs）的小细胞外囊泡（sEVs）的抗炎特性。在用链脲佐菌素（STZ）诱导糖尿病的大鼠发生DR后，用不同浓度的hUCMSC-sEVs治疗DR大鼠。我们的结果表明，用hUCMSC-sEVs治疗DR大鼠的视网膜不仅降低了大鼠视网膜中的血管渗漏水平，还降低了视网膜厚度以及相关炎症。此外，我们的体外证据表明，hUCMSC-sEVs可抑制高糖（HG）诱导的细胞炎症和凋亡。随后，我们通过微阵列分析了hUCMSC-sEVs中差异表达的 microRNA（miRNA），并进行了计算机模拟研究以预测miR-18b的靶mRNA。我们的研究结果还显示，sEV治疗后糖尿病大鼠视网膜中miR-18b的表达显著升高。此外，发现miR-18b靶向丝裂原活化蛋白激酶激酶激酶1（MAP3K1），从而抑制NF-κB p65磷酸化以减轻DR。总体而言，本研究突出了hUCMSCs-sEVs作为通过转移miR-18b在DR中发挥抗炎和抗凋亡作用的生物材料的潜力。
