{"id":254,"title":"Curcumin inhibits angiogenesis in endometriosis by regulating miR-495-3p expression in M2 macrophage-derived sEVs","title_zh":"姜黄素通过调控M2巨噬细胞来源sEVs中miR-495-3p抑制子宫内膜异位症血管生成","url":"https://pubmed.ncbi.nlm.nih.gov/42976742","doi":"10.1016/j.intimp.2026.117615","pmid":"42976742","journal":"Int Immunopharmacol","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Mei S","Ding J","Zhao Q","Li Y","Wang X","Ni Z","Yu C"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":4.0,"hits":["endometriosis"]},{"slug":"repro-immunology","score":4.0,"hits":["macrophage"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":76.0,"final_score":76.0,"score_dims":{"novelty":76,"rigor":78,"impact":70,"relevance":72,"translation":66},"recommend_reason":"机制链条较完整（动物模型—巨噬细胞极化—sEV miRNA—内皮功能—靶基因），为子宫内膜异位症抗血管生成提供新靶点；但尚属基础研究，样本量与临床转化证据有限，适合关注内异症/生殖免疫者阅读。","keywords":["姜黄素","子宫内膜异位症","小细胞外囊泡","miR-495-3p","巨噬细胞极化","血管生成"],"selected":1,"story_id":143,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该研究在小鼠子宫内膜异位症模型中观察姜黄素对病灶及局部血管生成的影响，并用HUVECs、人腹腔巨噬细胞及THP-1/RAW264.7来源小细胞外囊泡(sEVs)共培养体系探讨机制。结果显示，低剂量姜黄素(10 μM)通过促使巨噬细胞向M1样极化、改变sEVs miRNA载物，上调sEVs中miR-495-3p，进而抑制HUVEC增殖、迁移和成管；BMI1被鉴定为miR-495-3p直接靶点。结论提示巨噬细胞-sEV-血管生成轴可能是EMs治疗靶点。","summary":"BACKGROUND: Endometriosis (EMs) is a common and challenging condition affecting women of reproductive age. Local vascularisation of ectopic lesions is a key driver of disease progression, and effective anti-angiogenic therapies remain limited. Curcumin has shown therapeutic efficacy against endometriotic lesions; however, the mechanism underlying its inhibition of angiogenesis remains unclear. METHODS: A mouse EMs model was established to evaluate the in vivo effects of curcumin on ectopic lesion formation and local angiogenesis. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were performed to determine the optimal inhibitory concentration of curcumin. Small extracellular vesicles (sEVs) were isolated and characterised from human peritoneal macrophages and from the THP-1 and RAW264.7 cell lines. A co-culture system was employed to assess whether curcumin regulates macrophage polarisation and thereby alters the effects of macrophage-derived sEVs on HUVEC angiogenesis. Differentially expressed miRNAs were identified by high-throughput miRNA sequencing and bioinformatic analysis, followed by functional validation of key candidates. RESULTS: In vivo, curcumin administration significantly reduced the size, volume, and adhesion of endometriotic lesions and suppressed local angiogenesis. In vitro, direct inhibition of HUVEC angiogenesis required 30 μM curcumin, whereas a lower concentration (10 μM) effectively modulated macrophage-derived sEVs to produce comparable anti-angiogenic effects. This treatment significantly reversed the pro-angiogenic activity of sEVs derived from EMs patients. Mechanistically, treatment with 10 μM curcumin was associated with a shift towards an M1-like macrophage phenotype and altered sEVs' activity. This change altered sEVs' cargo and subsequently inhibited HUVEC tube formation. miRNA sequencing identified miR-495-3p as a key mediator. Curcumin treatment significantly increased miR-495-3p levels in macrophage-derived sEVs. Functional assays demonstrated that inhibition of miR-495-3p partially restored HUVEC proliferation, migration, and tube formation suppressed by sEVs from curcumin-treated macrophages. While bioinformatic prediction and dual-luciferase reporter analysis identified BMI1 as a direct target and potential downstream effector of miR-495-3p. CONCLUSIONS: Curcumin suppresses EMs progression by regulating macrophage polarisation and modifying sEVs' miRNA expression profiles. Its anti-angiogenic effect is mediated, at least in part, by upregulation of macrophage-derived sEVs' miR-495-3p. BMI1 was a direct target and potential downstream effector of miR-495-3p. These findings provide molecular evidence for the anti-angiogenic activity of curcumin and identify the macrophage-sEV-angiogenesis axis as a potential therapeutic target for EMs.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}