Cao Xin, Song Yu, Huang Li-Li, Tian Ya-Jing, Wang Xiao-Le, Hua Ling-Yan
Department of Ophthalmology, Affiliated Hospital 2 of Nantong University, the first people's hospital of Nantong, Nantong 226000, Jiangsu Province, PR China.
Department of Ophthalmology, Affiliated Hospital 2 of Nantong University, the first people's hospital of Nantong, Nantong 226000, Jiangsu Province, PR China.
Genomics. 2022 Nov;114(6):110498. doi: 10.1016/j.ygeno.2022.110498. Epub 2022 Sep 26.
Diabetic retinopathy is one of the microvascular complications in diabetic patients and the leading cause of blindness worldwide. The levels of METTL3, lncRNA SNHG7, KHSRP, MKL1, endothelial and mesenchymal markers were determined by RT-qPCR or western blot assays in vitro and in vivo. H&E staining was used to observe the retinal structure in a mouse model of DR. The expression levels of METTL3 and SNHG7 were significantly downregulated in DR patients, DR mice and high glucose-induced HRMECs cells. Notably, METTL3 installed the m6A modification and enhanced the stability of SNHG7. Besides, METTL3 inhibited HRMECs EndoMT by promoting the expression of SNHG7. Additionally, SNHG7 was found to weaken MKL1 mRNA stability by binding to the RNA-binding protein KHSRP. Furthermore, we verified that METTL3 regulated EndoMT in DR through the SNHG7/MKL1 axis. We conclude that METTL3 regulates endothelial-mesenchymal transition in DR via the SNHG7/KHSRP/MKL1 axis, providing a new target for DR treatment.
糖尿病视网膜病变是糖尿病患者的微血管并发症之一，也是全球失明的主要原因。通过体外和体内的逆转录定量聚合酶链反应（RT-qPCR）或蛋白质免疫印迹分析来测定METTL3、长链非编码RNA SNHG7、KH型剪接调节蛋白（KHSRP）、心肌素相关转录因子1（MKL1）、内皮细胞和间充质细胞标志物的水平。苏木精-伊红（H&E）染色用于观察糖尿病视网膜病变小鼠模型中的视网膜结构。在糖尿病视网膜病变患者、糖尿病视网膜病变小鼠和高糖诱导的人视网膜微血管内皮细胞（HRMECs）中，METTL3和SNHG7的表达水平显著下调。值得注意的是，METTL3进行N6-甲基腺苷（m6A）修饰并增强了SNHG7的稳定性。此外，METTL3通过促进SNHG7的表达来抑制人视网膜微血管内皮细胞的内皮-间充质转化（EndoMT）。此外，发现SNHG7通过与RNA结合蛋白KHSRP结合来削弱MKL1信使核糖核酸（mRNA）的稳定性。此外，我们证实METTL3通过SNHG7/MKL1轴在糖尿病视网膜病变中调节内皮-间充质转化。我们得出结论，METTL3通过SNHG7/KHSRP/MKL1轴调节糖尿病视网膜病变中的内皮-间充质转化，为糖尿病视网膜病变的治疗提供了新靶点。
