在糖尿病脏病患者中,TRAIL通过死亡受体5诱导 podocyte PANoptosis
Zhimei Lv1, Jinxiu Hu1, Hong Su1
1Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Kidney international
|November 21, 2024
概括
糖尿病病 (DKD) 涉及细胞损失. 在DKD中,TRAIL (TNFSF10) 和DR5 (TNFRSF10B) 信号驱动Podocyte PANoptosis,这表明功能衰竭的治疗标.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 糖尿病病 (DKD) 是导致衰竭的主要原因,其特点是受细胞损伤和损失.
- 细胞细胞死亡,包括PANoptosis (亡,亡和亡),有助于DKD的进展.
研究的目的:
- 调查与瘤坏死因子 (TNF) 相关的诱导亡联体 (TRAIL) 和其受体,死亡受体5 (DR5) 在DKD中细胞损伤中的作用.
- 探索针对DKD中的TRAIL/DR5途径的治疗潜力.
主要方法:
- 人类脏样本的单细胞RNA测序 (scRNA-seq) 用于比较正常和DKD组织.
- 在体外研究中,使用培养的人类受体细胞,用TNF-α,TRAIL或DR5激活剂/抑制剂治疗.
- 在体内研究涉及基因改造小鼠与 podocyte 特定的删除或过度表达 TNFSF10 / TNFRSF10B,并用DR5 抑制剂治疗.
主要成果:
- 在 DKD 患者的 podocytes 中观察到 TRAIL (TNFSF10) 和 DR5 (TNFRSF10B) 的表达增加,与疾病严重程度相关.
- 在培养下细胞中,TNF-α刺激上调了 TRAIL 和 DR5,促进了 PANoptosis.
- 抑制 TRAIL 或 DR5 在体外减轻了 podocyte PANoptosis,而它们的激活则增强了它.
- 在DKD的小鼠模型中,TNFSF10或TNFRSF10B保护损伤的细胞特异性删除.
- 细胞中TNFSF10的过度表达加剧了DKD表型,而DR5抑制减少了白膜尿和球损伤.
结论:
- 在DKD中,TRAIL/DR5信号通路在调解 podocyte 损伤和 PANoptosis 中发挥着关键的自身分泌作用.
- 针对TRAIL/DR5轴是一个有前途的治疗策略,用于管理DKD和预防功能衰竭.
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