{"id":218,"title":"Mast Cell-Derived CCL2 Exacerbates Endometriosis Pain via Binding to CCR4","title_zh":"肥大细胞来源CCL2通过结合神经元CCR4加剧子宫内膜异位症疼痛","url":"https://pubmed.ncbi.nlm.nih.gov/42992652","doi":"10.1177/15578100261503774","pmid":"42992652","journal":"OMICS","kind":"paper","lang":"en","published_at":"2026-11-06T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Deng Y","Chen P","Ding H"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":6.0,"hits":["endometrial","endometriosis","stromal cell"]},{"slug":"omics-methods","score":1.0,"hits":["scrna-seq"]}],"topic_score":6.0,"preference_score":0.0,"preference_labels":[],"llm_score":73.0,"final_score":73.0,"score_dims":{"novelty":74,"rigor":78,"impact":66,"relevance":68,"translation":66},"recommend_reason":"机制链条完整（单细胞定位—临床组织相关性—共培养—大鼠模型验证），为EMs相关疼痛提供CCL2/CCR4新靶点；与辅助生殖的核心环节（胚胎、卵巢）关联较间接，但对合并内异症的助孕人群疼痛管理有参考价值。","keywords":["子宫内膜异位症","CCL2/CCR4","肥大细胞","神经敏化","疼痛","单细胞转录组"],"selected":1,"story_id":22,"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":"研究探讨肥大细胞及CCL2在子宫内膜异位症（EMs）疼痛神经敏化中的作用。作者先利用公共单细胞数据集（GSE179640）定位CCL2在EMs各细胞类型的表达，并验证其在肥大细胞中富集；随后采集EMs患者异位与在位内膜及对照正常内膜，检测CCL2、CCR4、肥大细胞数量与PGP9.5阳性神经纤维，并与疼痛评分作相关分析；建立内膜间质细胞—肥大细胞—神经元共培养体系，并在EMs大鼠模型中评估痛阈与病灶神经纤维密度。结果显示CCL2在EMs中显著上调，并与疼痛、肥大细胞浸润及感觉神经相关；抑制CCR4可缓解大鼠痛觉过敏并减少病灶神经纤维，提示肥大细胞来源CCL2经神经元CCR4促进神经敏化，是潜在的镇痛靶点。","summary":"Endometriosis (EMs) pain severely reduces patients' quality of life, but its underlying mechanisms are not fully understood. Mast cells and C-C motif chemokine ligand 2 (CCL2) are highly abundant in EMs lesions, yet their roles in neural sensitization remain unclear. Bioinformatics analysis of a public scRNA-seq dataset (GSE179640) was performed to define CCL2 expression across EMs cell types and its enrichment in mast cells. We collected ectopic and eutopic endometrial tissues from EMs patients and normal endometrial tissues from controls. CCL2, C-C chemokine receptor type 4 (CCR4) expression, mast cell numbers, and protein gene product 9.5-positive nerve fibers were measured and correlated with pain. In vitro coculture models of endometrial stromal cells, mast cells, and neurons were established, and related functions were examined. An in vivo EMs rat model was used to assess pain thresholds and nerve fiber density. CCL2 was significantly upregulated in EMs and positively correlated with pain, mast cell infiltration, and sensory nerves. Stromal cell-mast cell coculture increased CCL2. CCL2 knockdown in mast cells inhibited degranulation and migration but promoted neurite outgrowth, nerve growth factor expression, and calcium influx in neurons. Inhibiting CCR4 relieved hyperalgesia and reduced lesion nerve fibers in rats. Mast cell-derived CCL2 promotes neural sensitization by activating neuronal CCR4, which contributes to EMs pain. Targeting CCL2/CCR4 may serve as a new therapeutic approach for EMs pain.","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}}