Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.
Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.
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DOI：
10.1172/jci.insight.166012
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发表时间：
2023-05-22
期刊：
影响因子：
8
通讯作者：
Chugh, Sumant S.
中科院分区：
文献类型：
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作者：
Avila, Maria Del Nogal;Das, Ranjan;Kharlyngdoh, Joubert;Molina-Jijon, Eduardo;Blazquez, Hector Donoro;Gambut, Stephanie;Crowley, Michael;Crossman, David K.;Gbadagesin, Rasheed A.;Chugh, Sunveer S.;Chugh, Sunjeet S.;Avila-Casado, Carmen;Mace, Camille;Clement, Lionel C.;Chugh, Sumant S.
像SARS-CoV-2这样的病毒性疾病在没有直接病毒感染的情况下对非呼吸器官具有病理影响。我们给小鼠注射了啮齿类动物的混合物，这些混合物相当于由SARS-CoV-2/COVID-19或鼻病毒普通感冒感染引起的人类细胞因子风暴。在低剂量下，COVID-19鸡尾酒在锌指和同源异型盒2（Zhx 2）亚型和Zhx 2 +/+小鼠中诱导肾小球损伤和蛋白尿，以模拟COVID-19相关的蛋白尿。普通感冒鸡尾酒在Zhx 2低形态小鼠中选择性诱导白蛋白尿，以建立微小病变疾病复发模型，在TNF-α、可溶性IL-4 R α或IL-6耗竭后改善。Zhx 2亚型状态增加了足细胞ZHX蛋白在体内（两种混合物）的细胞膜到核的迁移，并降低了体外磷酸化STAT 6激活（COVID-19混合物）。在较高剂量下，COVID-19鸡尾酒诱导了Zhx 2 +/+小鼠的急性心脏损伤、心肌炎、心包炎、急性肝损伤、急性肾损伤和高死亡率，而Zhx 2亚型小鼠相对受到保护，部分原因是这些器官中的STAT 5和STAT 6通路早期异步激活。在Zhx 2 +/+小鼠中，TNF-α与IL-2、IL-13或IL-4的细胞因子组合的双重耗竭减少了多器官损伤并消除了死亡率。使用基因组测序和CRISPR/Cas9，ZHX 2上游的插入被鉴定为人类ZHX 2亚型状态的原因。
Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus common cold infection. At low doses, COVID-19 cocktails induced glomerular injury and albuminuria in zinc fingers and homeoboxes 2 (Zhx2) hypomorph and Zhx2+/+ mice to mimic COVID-19–related proteinuria. Common Cold cocktail induced albuminuria selectively in Zhx2 hypomorph mice to model relapse of minimal change disease, which improved after depletion of TNF-α, soluble IL-4Rα, or IL-6. The Zhx2 hypomorph state increased cell membrane to nuclear migration of podocyte ZHX proteins in vivo (both cocktails) and lowered phosphorylated STAT6 activation (COVID-19 cocktail) in vitro. At higher doses, COVID-19 cocktails induced acute heart injury, myocarditis, pericarditis, acute liver injury, acute kidney injury, and high mortality in Zhx2+/+ mice, whereas Zhx2 hypomorph mice were relatively protected, due in part to early, asynchronous activation of STAT5 and STAT6 pathways in these organs. Dual depletion of cytokine combinations of TNF-α with IL-2, IL-13, or IL-4 in Zhx2+/+ mice reduced multiorgan injury and eliminated mortality. Using genome sequencing and CRISPR/Cas9, an insertion upstream of ZHX2 was identified as a cause of the human ZHX2 hypomorph state.
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DOI：
10.1053/j.ajkd.2009.03.019
发表时间：
2009-11
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Abdel-Hafez M;Shimada M;Lee PY;Johnson RJ;Garin EH
通讯作者：
Garin EH
影响因子：
5.1
作者：
Jiang, Jieyun;Turpin, Courtney;Qiu, Guofang (Shirley);Xu, Mei;Lee, Eun;Hinds, Terry D., Jr.;Peterson, Martha L.;Spear, Brett T.
通讯作者：
Spear, Brett T.
影响因子：
3.7
作者：
Clarke NE;Fisher MJ;Porter KE;Lambert DW;Turner AJ
通讯作者：
Turner AJ
影响因子：
37.8
作者：
Bozkurt, Biykem;Kamat, Ishan;Hotez, Peter J.
通讯作者：
Hotez, Peter J.
影响因子：
19.6
作者：
Chugh, S;Yuan, HP;Salant, DJ
通讯作者：
Salant, DJ