足细胞中高迁移率族蛋白 B1 的释放加剧脂多糖诱导的急性肾损伤。
Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury.
机构信息
Department of Nephrology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, 441000 Hubei, China.
Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Rd., Wuhan, 430060 Hubei, China.
出版信息
Mediators Inflamm. 2021 Sep 27;2021:5220226. doi: 10.1155/2021/5220226. eCollection 2021.
OBJECTIVE
Acute kidney injury (AKI) usually occurs during sepsis. Inflammation factors, such as high-mobility group box 1 (HMGB1), are dramatically upregulated under septic conditions. In our current work, the functions of HMGB1 in AKI were explored.
METHODS
An AKI model was induced by the lipopolysaccharide (LPS) challenge in C57 mice. Podocytes were challenged by LPS for different durations. Subsequently, podocytes transfected with HMGB1 siRNA were exposed to LPS for 24 h. The expressions of supernatant HMGB1 and cellular active caspase-3 were examined by Western blotting analysis. To explore the effect of HMGB1 on tubular epithelial cells (TECs), HK-2 cells were exposed to HMGB1 at various concentrations for 24 h. Epithelial-mesenchymal transition (EMT) of HK-2 cells was evaluated by Western blotting analysis. Mitochondrial division and apoptosis of HK-2 cells were assessed by MitoTracker Red and Western blotting analysis, respectively.
RESULTS
Compared with the sham control group, the expression of HMGB1 was increased in the kidney of AKI mice. Moreover, the expression of supernatant HMGB1 was increased in LPS-challenged podocytes compared with the control group. Knockdown of HMGB1 attenuated LPS-induced podocyte injury. Besides, EMT in TECs was triggered by HMGB1. Mitochondrial damage and apoptosis of HK-2 cells exposed to HMGB1 were markedly elevated compared with the control group.
CONCLUSIONS
Collectively, HMGB1 release in podocytes was induced by LPS, subsequently leading to exacerbated AKI.
目的
急性肾损伤（AKI）通常发生在脓毒症期间。在脓毒症条件下，高迁移率族蛋白 B1（HMGB1）等炎症因子的表达显著上调。在本研究中，我们探讨了 HMGB1 在 AKI 中的作用。
方法
采用脂多糖（LPS）刺激 C57 小鼠建立 AKI 模型。用 LPS 刺激足细胞不同时间。然后，用 LPS 处理转染 HMGB1 siRNA 的足细胞 24 小时。通过 Western blot 分析检测上清液 HMGB1 和细胞内活性 caspase-3 的表达。为了探讨 HMGB1 对肾小管上皮细胞（TECs）的影响，将 HK-2 细胞分别用不同浓度的 HMGB1 处理 24 小时。通过 Western blot 分析评估 HK-2 细胞上皮-间充质转化（EMT）。通过 MitoTracker Red 和 Western blot 分析分别评估 HK-2 细胞线粒体分裂和凋亡。
结果
与假手术对照组相比，AKI 小鼠肾脏中 HMGB1 的表达增加。此外，与对照组相比，LPS 刺激的足细胞上清液中 HMGB1 的表达增加。敲低 HMGB1 可减轻 LPS 诱导的足细胞损伤。此外，HMGB1 可触发 TECs 的 EMT。与对照组相比，暴露于 HMGB1 的 HK-2 细胞的线粒体损伤和凋亡明显增加。
结论
总之，LPS 诱导的足细胞中 HMGB1 的释放导致 AKI 加重。
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