通过促进Hif-1α介导的葡萄糖分解来促进M1极化,Irf7使前列腺炎恶化
Tong Meng1,2, Yi Zhang1,2, Huihui Wang1,2
1Department of Urology, Institute of Urology, Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, Anhui Province, 230022, People's Republic of China.
Cellular and molecular life sciences : CMLS
|February 22, 2025
概括
干扰素调节因子7 (Irf7) 驱动慢性前列腺炎/慢性骨盆疼痛综合征 (CP/CPPS) 通过增加M1巨细胞两极分化和前列腺纤维化. 向Irf7可能为CP/CPPS提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 分子生物学分子生物学
背景情况:
- 慢性前列腺炎/慢性骨盆疼痛综合征 (CP/CPPS) 是一种普遍存在的疾病,其特征是骨盆疼痛和排泄功能障碍.
- 亲炎性M1巨细胞在启动CP/CPPS中起着关键作用.
- 已知干扰素调节因子7 (Irf7) 在自身免疫性疾病中促进M1两极分化,但其在CP/CPPS中的作用尚不清楚.
研究的目的:
- 调查Irf7在实验性自身免疫性前列腺炎 (EAP) 的发展和进展中的作用, CP/CPPS.的一个模型.
- 要确定Irf7是否通过通过Hif-1α增强糖解和M1极化来加剧EAP.
- 探索Irf7作为CP/CPPS的潜在治疗点.
主要方法:
- 建立了一个实验性自身免疫性前列腺炎 (EAP) 鼠标模型.
- 分析了前列腺炎症,Irf7表达,糖解和M1极化.
- 使用了sh-Irf7干预,Hif-1α激动剂和体外M1极化试验.
- 雇佣了ChIP和双化酶报告员试验,以调查Irf7-Hif-1α促进体相互作用.
主要成果:
- 在EAP模型中观察到升高的Irf7表达.
- 通过抑制Hif-1α核转位,减少Irf7降低了M1细胞糖解和M1极化.
- 在巨细胞中,Irf7直接与Hif-1α促进体相互作用.
- 通过IRF7 Knockdown可减少前列腺组织纤维化.
结论:
- 通过增强M1极化和前列腺纤维化,Irf7促进CP/CPPS的发展和进展.
- 这是由Irf7诱导的Hif-1α转录的上调调节和随后的糖分解增加的介导.
- 向Irf7为CP/CPPS提供了一个新的治疗策略.
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