Department of Ophthalmology, Kashgar Prefecture Second People's Hospital, Kashgar, 844000, Xinjiang, China.
Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, No. 1 Youyi Road, Yuzhong District, Chongqing, China.
Graefes Arch Clin Exp Ophthalmol. 2023 Sep;261(9):2547-2555. doi: 10.1007/s00417-023-06065-6. Epub 2023 Apr 20.
To explore whether Fork head box protein M1 (FOXM1) is involved in TGF-β2-induced injury of human lens epithelial cells and its related mechanism.
Human lens epithelium samples from cataract patients and healthy controls were collected. A cellular epithelial injury model was established by treating HLE-B3 cells with TGF-β2. QPCR, immunoblot assays were performed to detect the levels of FOXM1 in human cataract samples and the lens epithelial injury cell model. FOXM1 siRNA and pcDNA3.1-FOXM1 plasmids were transfected into the cells to knockdown and overexpress FOXM1, respectively. MTT and wound closure and transwell assays were performed to analyze cell proliferation and migration in HLE-B3 cells. Immunoblot assays were also conducted to detect the effects of FOXM1 on EMT, VEGFA and MAPK/ERK signaling.
We found high expression of FOXM1 in lens tissues of cataract patients. Silencing of FOXM1 in TGF-β2-induced HLE-B3 cells suppressed cell proliferation, migration, and the EMT process. Mechanistically, we found that downregulation of FOXM1 inhibited the VEGFA/MAPK signaling pathway in TGF-β2-induced HLE-B3 cells.
FOXM1 promoted TGF-β2-induced injury of human lens epithelial cells (hLECs) by promoting VEGFA expression. FOXM1 could be a potential drug target for the treatment of ocular diseases.
探讨叉头框蛋白 M1（FOXM1）是否参与转化生长因子-β2（TGF-β2）诱导的人晶状体上皮细胞损伤及其相关机制。
收集白内障患者和健康对照者的人晶状体上皮细胞样本。用 TGF-β2 处理 HLE-B3 细胞建立细胞上皮损伤模型。通过 QPCR 和免疫印迹实验检测人白内障样本和晶状体上皮损伤细胞模型中 FOXM1 的水平。FOXM1 siRNA 和 pcDNA3.1-FOXM1 质粒分别转染入细胞以敲低和过表达 FOXM1。MTT 法、划痕愈合实验和 Transwell 实验分析 HLE-B3 细胞的增殖和迁移。免疫印迹实验还检测了 FOXM1 对上皮间质转化（EMT）、VEGFA 和 MAPK/ERK 信号通路的影响。
我们发现白内障患者晶状体组织中 FOXM1 高表达。在 TGF-β2 诱导的 HLE-B3 细胞中沉默 FOXM1 抑制细胞增殖、迁移和 EMT 过程。机制上，我们发现下调 FOXM1 抑制了 TGF-β2 诱导的 HLE-B3 细胞中 VEGFA/MAPK 信号通路。
FOXM1 通过促进 VEGFA 表达促进 TGF-β2 诱导的人晶状体上皮细胞（hLECs）损伤。FOXM1 可能成为眼部疾病治疗的潜在药物靶点。
