Rubicon-deficiency sensitizes mice to mixed lineage kinase domain-like (MLKL)-mediated kidney ischemia-reperfusion injury.
Rubicon-deficiency sensitizes mice to mixed lineage kinase domain-like (MLKL)-mediated kidney ischemia-reperfusion injury.
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DOI：
10.1038/s41419-022-04682-3
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发表时间：
2022-03-14
影响因子：
9
通讯作者：
Linkermann A
中科院分区：
文献类型：
--
作者：
Tonnus W;Locke S;Meyer C;Maremonti F;Eggert L;von Mässenhausen A;Bornstein SR;Green DR;Linkermann A
胞浆蛋白Rubcon(RUBCN)在清除坏死性碎片和自身免疫中起重要作用。然而，RUBCN在急性肾损伤(AKI)模型中的作用尚未被研究，AKI是一种典型的涉及肾小管坏死的疾病。在这里，我们证明RUBCN缺陷小鼠对缺血-再灌注损伤(IRI)和顺铂诱导的AKI引起的肾脏损伤高度敏感。在IRI模型中，RUBCN和混合谱系激酶结构域(MLKL)的联合缺失部分逆转了该模型的敏感性，这表明RUBCN的缺失在该模型中对坏死性下垂敏感。已知坏死性下垂与肿瘤坏死因子α诱导的严重炎症反应综合征(SIRS)有关，但我们发现注射肿瘤坏死因子α对RUBCN缺陷小鼠的总存活率没有统计学意义上的差异。我们还产生了RUBCN缺陷小鼠，该小鼠缺乏Gasdermin D(GSDMD)，GSDMD是松果体下垂的终末介质，但没有观察到AKI表型逆转。最后，与先前对RUBCN作用的理解相反，我们没有在RUBCN缺陷小鼠中发现显著的自身免疫表型，但在老年RUBCN缺陷小鼠中检测到了慢性肾损伤(CKD)，无论性别。综上所述，我们的数据表明RUBCN缺陷小鼠对肾脏损伤高度敏感。
The cytosolic protein rubicon (RUBCN) has been implicated in the removal of necrotic debris and autoimmunity. However, the role of RUBCN in models of acute kidney injury (AKI), a condition that typically involves necrotic kidney tubules, was not investigated. Here, we demonstrate that RUBCN-deficient mice are hypersensitive to renal damage induced by ischemia-reperfusion injury (IRI) and cisplatin-induced AKI. Combined deficiency of RUBCN and mixed lineage kinase domain-like (MLKL) partially reversed the sensitivity in the IRI model suggesting that the absence of RUBCN sensitizes to necroptosis in that model. Necroptosis is known to contribute to TNFα-induced severe inflammatory response syndrome (SIRS), but we detected no statistically significant difference in overall survival following injection of TNFα in RUBCN-deficient mice. We additionally generated RUBCN-deficient mice which lack gasdermin D (GSDMD), the terminal mediator of pyroptosis, but no reversal of the AKI phenotype was observed. Finally, and in contrast to the previous understanding of the role of RUBCN, we did not find a significant autoimmune phenotype in RUBCN-deficient mice, but detected chronic kidney injury (CKD) in aged RUBCN-deficient mice of both sexes. In summary, our data indicate that RUBCN-deficient mice are hypersensitive to kidney injury.
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影响因子：
3.3
作者：
Tabata K;Matsunaga K;Sakane A;Sasaki T;Noda T;Yoshimori T
通讯作者：
Yoshimori T
影响因子：
28.3
作者：
Li T;Kong L;Li X;Wu S;Attri KS;Li Y;Gong W;Zhao B;Li L;Herring LE;Asara JM;Xu L;Luo X;Lei YL;Ma Q;Seveau S;Gunn JS;Cheng X;Singh PK;Green DR;Wang H;Wen H
通讯作者：
Wen H
RGMb 通过 MLKL 依赖性机制抑制肾小管细胞坏死性凋亡，从而预防急性肾损伤
DOI：
10.1073/pnas.1716959115
发表时间：
2018-02-13
影响因子：
11.1
作者：
Liu, Wenjing;Chen, Binbin;Xia, Yin
通讯作者：
Xia, Yin
影响因子：
64.8
作者：
Shi, Jianjin;Zhao, Yue;Shao, Feng
通讯作者：
Shao, Feng
影响因子：
19.6
作者：
Linkermann, Andreas;Braesen, Jan H.;Krautwald, Stefan
通讯作者：
Krautwald, Stefan