{"title":"星形胶质细胞升高基因-1对视网膜光感受器凋亡和炎症的抑制作用","authors":"Xinran Gao , Haoran Qiao","doi":"10.1016/j.imbio.2025.152889","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.</div></div><div><h3>Methods</h3><div>The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.</div></div><div><h3>Results</h3><div>AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.</div></div><div><h3>Conclusions</h3><div>AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152889"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Suppression of astrocyte elevated gene-1 protects against light-induced photoreceptor apoptosis and inflammation in retina\",\"authors\":\"Xinran Gao , Haoran Qiao\",\"doi\":\"10.1016/j.imbio.2025.152889\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.</div></div><div><h3>Methods</h3><div>The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.</div></div><div><h3>Results</h3><div>AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.</div></div><div><h3>Conclusions</h3><div>AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.</div></div>\",\"PeriodicalId\":13270,\"journal\":{\"name\":\"Immunobiology\",\"volume\":\"230 3\",\"pages\":\"Article 152889\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-03-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0171298525000233\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0171298525000233","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Suppression of astrocyte elevated gene-1 protects against light-induced photoreceptor apoptosis and inflammation in retina
Purpose
To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.
Methods
The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.
Results
AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.
Conclusions
AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.
期刊介绍:
Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including
• Innate Immunity,
• Adaptive Immunity,
• Complement Biology,
• Macrophage and Dendritic Cell Biology,
• Parasite Immunology,
• Tumour Immunology,
• Clinical Immunology,
• Immunogenetics,
• Immunotherapy and
• Immunopathology of infectious, allergic and autoimmune disease.