Migration and proliferation of human retinal pigment epithelium

人视网膜色素上皮的迁移和增殖

• 批准号: 7594093
• 负责人: sheldon s miller
• 金额: $ 58.41万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594093
• 关键词: Affect; Apical; Apoptosis; Bathing; Cell Proliferation; Cells; Choroid; Complex; Condition; Cytoskeleton; Epithelial; Functional disorder; Growth Factor; Human; Inflammation; Inflammatory; Interferons; Mediating; Protein Isoforms; Retina; Retinal Pigments; Role; Structure of retinal pigment epithelium; Tight Junctions; Wound Healing; apical membrane; cell motility; cytokine; fetal; inhibitor/antagonist; migration; monolayer; platelet-derived growth factor BB; platelet-derived growth factor C; response

PDGF-C and -D are the major isoforms expressed in human retinal pigment epithelium (RPE). Functionally active PDGFR-α and -β are mainly expressed at the apical membrane. PDGF-BB, -CC, -DD significantly increased proliferation while PDGF-BB, -AB and -DD significantly increased cell migration, suggesting a critical role in RPE pathophysiology. A pro-inflammatory cytokine mixture (TNFα/IL-1β/IFNγ) abrogated PDGF-induced proliferation and migration by inducing apoptosis, and by disrupting the cytoskeleton and tight junctions. Further study demonstrated that IFNγ alone significantly inhibited human fetal RPE (hfRPE) proliferation, which was significantly blocked by JAK inhibitor I, while Type I IFN, IFNα and IFNβ did not affect hfRPE proliferation under the same culture conditions. Addition of IFNγ to the basal, but not the apical bath significantly increased Jv across hfRPE monolayer. In contrast to hfRPE, the proinflammatory cytokine mixture, and IFNγ by itself, stimulated the proliferation of choroidal cells. These findings suggest a complex role of pro-inflammatory cytokines, particularly IFNγ, in overcoming local proliferative/wound healing responses of RPE at the retina/RPE/choroid interface.

PDGF-C和-D是人视网膜色素上皮(RPE)表达的主要亚型。具有功能活性的PDGFR和PDGFR主要在顶膜表达。PDGF-BB、-CC、-DD显著促进细胞增殖，PDGF-BB、-AB、-DD显著促进细胞迁移，提示PDGF-BB、-CC、-DD在RPE病理生理过程中起重要作用。促炎细胞因子混合物(肿瘤坏死因子/白介素1/干扰素)通过诱导细胞凋亡、破坏细胞骨架和紧密连接来抑制PDGF诱导的增殖和迁移。进一步研究表明，在相同的培养条件下，单独使用干扰素可显著抑制人胎儿RPE(HfRPE)的增殖，这种抑制作用可被JAK抑制剂I显著阻断，而I型干扰素、干扰素和干扰素对hfRPE的增殖无明显影响。在基础浴液中加入干扰素，而不是在顶端浴液中加入干扰素，可显著增加hfRPE单层的JV。与促炎症细胞因子混合物hfRPE相比，干扰素本身可以刺激脉络膜细胞的增殖。这些发现表明，促炎症细胞因子，特别是干扰素，在克服视网膜/RPE/脉络膜界面的RPE局部增殖/伤口愈合反应方面具有复杂的作用。