在暴露于西斯后,慢性炎症和损伤中的STAT1/HMGB1/NF-κB通路
Ying Fu1, Yu Xiang1, Ying Wang1
1Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
Theranostics
|June 7, 2023
概括
重复低剂量西斯 (RLDC) 通过激活STAT1/HMGB1/NF-κB通路,导致脏损伤. 用HMGB1抗体阻断这种通路可能会保护脏免受慢性思思甲毒性影响.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 西斯普拉丁化疗可能会导致损伤 (毒性).
- 重复低剂量西斯 (RLDC) 减少了急性损伤,但可能导致慢性脏问题.
- 需要新的治疗点来预防长期的西斯普拉丁诱导的病.
研究的目的:
- 为了研究在西斯普拉丁脏毒性中的STAT1/HMGB1/NF-κB信号通路.
- 探索HMGB1作为预防RLDC慢性损伤的治疗标.
主要方法:
- 使用RLDC小鼠模型和近端管状细胞进行体内和体外研究.
- 使用中和抗体和淘汰技术检查了HMGB1的作用.
- 使用siRNA和药理学抑制剂 (Fludarabine) 调查了STAT1.
- 分析了基因表达综合 (GEO) 数据和人类脏活检样本.
主要成果:
- RLDC诱导管损伤,炎症和纤维化,并增加了HMGB1水平.
- 阻断HMGB1减少了NF-κB的激活,炎症,纤维化,并改善了功能.
- STAT1 knockdown抑制了HMGB1的转录和积累,这意味着STAT1参与了HMGB1的激活.
- 在慢性病 (CKD) 患者的脏组织中,STAT1/HMGB1/NF-κB轴被上调.
结论:
- 该STAT1/HMGB1/NF-κB通路驱动持续性炎症和纤维化后,西斯的毒性.
- 针对这种途径,特别是HMGB1,提供了一个潜在的策略,用于保护脏在青化疗期间.
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