LIGHT deficiency attenuates acute kidney disease development in an in vivo experimental renal ischemia and reperfusion injury model

作者全名："Zheng, Quan-you; Li, You; Liang, Shen-ju; Chen, Xi-ming; Tang, Ming; Rao, Zheng-sheng; Li, Gui-qing; Feng, Jian-Li; Zhong, Yu; Chen, Jian; Xu, Gui-lian; Zhang, Ke-qin"

作者地址："[Zheng, Quan-you; Feng, Jian-Li; Zhong, Yu] Army Med Univ, Hosp 958, Affiliated Hosp 1, Dept Urol, Chongqing 400020, Peoples R China; [Zheng, Quan-you; Li, You; Li, Gui-qing; Zhong, Yu; Chen, Jian; Xu, Gui-lian] Army Med Univ, Dept Immunol, Chongqing 400038, Peoples R China; [Li, You; Zhang, Ke-qin] Army Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing 400038, Peoples R China; [Li, You] Army Med Univ, Affiliated Hosp 3, Dept ICU, Chongqing 400042, Peoples R China; [Liang, Shen-ju] Army Med Univ, Affiliated Hosp 3, Dept Rheumatism & Immunol, Chongqing 400042, Peoples R China; [Chen, Xi-ming; Tang, Ming; Rao, Zheng-sheng; Zhang, Ke-qin] Chongqing Med Univ, Affiliated Hosp 2, Urinary Nephropathy Ctr, Chongqing 400065, Peoples R China"

通信作者："Xu, GL (通讯作者)，Army Med Univ, Dept Immunol, Chongqing 400038, Peoples R China.; Zhang, KQ (通讯作者)，Army Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing 400038, Peoples R China.; Zhang, KQ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Urinary Nephropathy Ctr, Chongqing 400065, Peoples R China."

来源：CELL DEATH DISCOVERY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000859876400002

JCR分区：Q2

影响因子：7

年份：2022

卷号：8

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Ischemia-reperfusion (I/R), a leading risk factor of acute kidney injury (AKI), is associated with high mortality and risk of progression to chronic kidney disease. However, the molecular mechanism of I/R-AKI remains not fully understood, which hinders its efficient clinical treatment. In this study, we observed that LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses. Consistently, blocking LIGHT signaling with its soluble receptor fusion proteins (HVEM-IgG-Fc or LT beta R-IgG-Fc) improved I/R renal dysfunction. RNA-sequencing and corresponding results indicated that LIGHT promoted oxidative stress and inflammation triggered by ischemic injury. Moreover, LIGHT signaling augmented ischemic stress-induced mitochondrial dysfunction characterized by an imbalance in mitochondrial fission and fusion, decreased mtDNA copies, impaired mitophagy, and increased mitochondrial membrane potential (Delta psi m). Mechanistically, LIGHT promoted mitochondrial fission by enhancing Drp1 phosphorylation (Ser616) and its translocation to the mitochondria. In conclusion, these results suggest that LIGHT-HVEM/LT beta R signaling is critical for the I/R-AKI pathogenesis and it is further confirmed to be related to the increase in I/R-induced oxidative stress and mitochondria dysfunction, which may be the underlying mechanism of LIGHT signaling-mediated I/R-AKI."

基金机构："National Natural Science Foundation of China [81670684, 81900628]; Youth Training Program of General Logistics Department Health Research Project [20QNPY033]; Military Medicine Youth Training Program of Army Medical University [2019XQN018]; New Clinical Technology Program for Military Medicine and War Trauma Treatment of Southwest Hospital [SWH2016JSTSYB38]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 81670684 and No. 81900628), Youth Training Program of General Logistics Department Health Research Project (20QNPY033), Military Medicine Youth Training Program of Army Medical University (2019XQN018) and New Clinical Technology Program for Military Medicine and War Trauma Treatment of Southwest Hospital (SWH2016JSTSYB38). We would like to thank Editage (www.editage.cn) for English language editing."