Kong Meng, Li Jingwen, Jin Rong, Zhang Yi, You Jia, Wang Nan, Tong Nianting
School of Medicine, Qingdao University, 266001, Qingdao, China; Department of Ophthalmology, Qingdao Municipal Hospital, 266001, Qingdao, China.
Department of Ophthalmology, Qingdao Municipal Hospital, 266001, Qingdao, China; Department of Pediatrics, Affiliated Hospital of Qingdao University, 266001, Qingdao, China.
Cell Stress Chaperones. 2025 May;30(3):130-142. doi: 10.1016/j.cstres.2025.03.002. Epub 2025 Mar 18.
The premature senescence of retinal pigment epithelium (RPE) plays a significant role in the development of age-related macular degeneration. This study aimed to investigate the potential protective effect of Lycium barbarum polysaccharide (LBP) against HO-induced premature senescence and to elucidate the underlying mechanisms. The ARPE-19 cell line was subjected to HO exposure to create a model of premature senescence. The modulation of microRNA-34a-5p expression was accomplished using antagomir and agomir, as assessed by quantitative real-time polymerase chain reaction. The senescence model was successfully established by treating cells with 200 μM HO for 2 hours daily over a span of three consecutive days. This oxidative stress resulted in a notable increase in the proportion of senescence-associated beta-galactosidase-positive cells, reaching 33.5%, without significant alterations in cell viability or apoptosis. In the ARPE-19 cells undergoing premature senescence, there was a marked increase in reactive oxygen species (ROS) production and malondialdehyde levels, coupled with a significant decrease in the activity of total superoxide dismutase, glutathione peroxidase, and catalase. Additionally, microRNA-34a-5p was found to be overexpressed in these cells. Treatment with LBP alleviated HO-induced premature senescence, diminished the overexpression of microRNA-34a-5p, and suppressed ROS production. Moreover, the incubation with ago-34a reversed the protective effect of LBP in ARPE-19 cells. In conclusion, the overexpression of microRNA-34a-5p contributes to the HO-induced premature senescence of ARPE-19 cells. LBP appears to mitigate this premature senescence, at least in part, by downregulating microRNA-34a-5p expression and reducing oxidative stress.
视网膜色素上皮(RPE)的过早衰老在年龄相关性黄斑变性的发展中起重要作用。本研究旨在探讨枸杞多糖(LBP)对过氧化氢(HO)诱导的过早衰老的潜在保护作用,并阐明其潜在机制。将ARPE-19细胞系暴露于HO以建立过早衰老模型。通过定量实时聚合酶链反应评估,使用抗miR和模拟miR来调节微小RNA-34a-5p的表达。通过连续三天每天用200μM HO处理细胞成功建立了衰老模型。这种氧化应激导致衰老相关β-半乳糖苷酶阳性细胞的比例显著增加,达到33.5%,而细胞活力或凋亡没有明显改变。在经历过早衰老的ARPE-19细胞中,活性氧(ROS)产生和丙二醛水平显著增加,同时总超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶的活性显著降低。此外,发现微小RNA-34a-5p在这些细胞中过表达。用LBP处理可减轻HO诱导的过早衰老,减少微小RNA-34a-5p的过表达,并抑制ROS产生。此外,用模拟miR-34a孵育可逆转LBP对ARPE-19细胞的保护作用。总之,微小RNA-34a-5p的过表达导致HO诱导的ARPE-19细胞过早衰老。LBP似乎至少部分地通过下调微小RNA-34a-5p表达和降低氧化应激来减轻这种过早衰老。