PARK7 is induced to protect against endotoxic acute kidney injury by suppressing NF-κB
PARK7 is induced to protect against endotoxic acute kidney injury by suppressing NF-κB
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PARK7 被诱导通过抑制 NF-κB 来防止内毒素性急性肾损伤
DOI：
10.1042/cs20220493
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发表时间：
2022
期刊：
影响因子：
6
通讯作者：
Zheng Dong
中科院分区：
文献类型：
--
作者：
Honglin Li;Zhiwen Liu;Ying Wang;Hui Wang;Juan Cai;Chengyuan Tang;Zheng Dong
脓毒症是急性肾损伤（AKI）的主要原因，而脓毒症 AKI 的发病机制尚不清楚。帕金森病蛋白 7 (PARK7) 是一种具有多种功能的蛋白，最近被认为与脓毒症 AKI 有关，但其潜在机制尚不清楚。在本研究中，我们确定了 PARK7 在脓毒症 AKI 中的作用，并进一步探讨了脂多糖 (LPS) 诱导的内毒素模型的潜在机制。 LPS 处理后，PARK7 在体内和体外均被诱导。与野生型（WT）小鼠相比，Park7缺陷小鼠在LPS治疗后肾组织损伤和功能障碍加重，肾小管凋亡和炎症增强。一致地，LPS 诱导的肾小管细胞体外凋亡和炎症因 Park7 敲低而加剧，而 PARK7 过表达则减轻。从机制上讲，LPS 处理期间沉默 Park7 促进了 p65（核因子 kappa B [NF-κB] 复合物的关键组成部分）的核转位和磷酸化，而 PARK7 过表达部分阻止了这些变化。此外，我们在肾小管细胞的细胞质中检测到 PARK7 与 p65 的相互作用，LPS 处理增强了这种相互作用。总的来说，这些发现表明 PARK7 被诱导通过抑制 NF-κB 信号传导来预防脓毒症 AKI。
Sepsis is a leading cause of acute kidney injury (AKI), and the pathogenesis of septic AKI remains largely unclear. Parkinson disease protein 7 (PARK7) is a protein of multiple functions that was recently implicated in septic AKI, but the underlying mechanism is unknown. In the present study, we determined the role of PARK7 in septic AKI and further explored the underlying mechanism in lipopolysaccharide (LPS)-induced endotoxic models. PARK7 was induced bothin vivoandin vitrofollowing LPS treatment. Compared with wild-type (WT) mice,Park7-deficient mice experienced aggravated kidney tissue damage and dysfunction, and enhanced tubular apoptosis and inflammation following LPS treatment. Consistently, LPS-induced apoptosis and inflammation in renal tubular cellsin vitrowere exacerbated byPark7knockdown, whereas they were alleviated by PARK7 overexpression. Mechanistically, silencingPark7facilitated nuclear translocation and phosphorylation of p65 (a key component of the nuclear factor kappa B [NF-κB] complex) during LPS treatment, whereas PARK7 overexpression partially prevented these changes. Moreover, we detected PARK7 interaction with p65 in the cytoplasm in renal tubular cells, which was enhanced by LPS treatment. Collectively, these findings suggest that PARK7 is induced to protect against septic AKI through suppressing NF-κB signaling.