Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies.
Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies.
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在COVID-19尸检中，肺细胞的特征是ER应激生物标志物GRP 78（SARS-CoV-2的共受体）的表达高度升高。
DOI：
10.1007/s12192-021-01230-4
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发表时间：
2021-09
影响因子：
3.8
通讯作者：
Benjamin IJ
中科院分区：
文献类型：
--
作者：
Puzyrenko A;Jacobs ER;Sun Y;Felix JC;Sheinin Y;Ge L;Lai S;Dai Q;Gantner BN;Nanchal R;North PE;Simpson PM;Rui H;Benjamin IJ
疫苗接种被广泛认为可以降低COVID-19的死亡率，但对SARS-CoV-2感染的发病率和死亡率的潜在宿主-病毒机制/相互作用仍知之甚少。急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是一种严重的肺损伤，其病理特征为肺泡损伤、炎症、非心源性水肿和透明膜形成。由于蛋白质抑制途径在细胞保护、免疫调节、蛋白质降解和组织修复中起着核心作用，我们使用替代生物标志物葡萄糖调节蛋白78（GRP 78）和SARS-CoV-2的辅助受体研究了未折叠蛋白反应（UPR）的病理学特征。尸检时，COVID-19肺的免疫染色显示，与非COVID对照肺相比，肺细胞和巨噬细胞中GRP 78的表达高度升高。GRP 78的表达在SARS-CoV-2感染和未感染的肺细胞中均被检测到，这是通过核衣壳蛋白的多重免疫染色确定的。在巨噬细胞中，来自死亡的COVID-19患者的GRP 78的免疫组织化学染色增加，但与来自非COVID-19对照的手术切除的GRP 78表达重叠。相比之下，来自COVID-19尸检的肺细胞的稳健原位GRP 78免疫染色与来自非COVID-19对照的肺细胞的原位GRP 78免疫染色相比没有显示出重叠，并且与年龄、种族/民族和性别无关。我们的研究结果为涉及与宿主恢复力有关的蛋白质抑制网络的应激反应途径带来了新的见解，并表明用现有疗法靶向GRP 78表达可能提供一种替代治疗策略来调节SARS-CoV-2感染期间的宿主-病毒相互作用。
Vaccinations are widely credited with reducing death rates from COVID-19, but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation, and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose-regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared with that of non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2-infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity, and gender compared with that from non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression with existing therapeutics might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.
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影响因子：
7.7
作者：
Zamorano Cuervo N;Grandvaux N
通讯作者：
Grandvaux N
影响因子：
8.8
作者：
Mastronardi, Maria Letizia;Mostefai, Hadj Ahmed;Andriantsitohaina, Ramaroson
通讯作者：
Andriantsitohaina, Ramaroson
DOI：
10.1164/rccm.200712-1835oc
发表时间：
2008-12-01
影响因子：
24.7
作者：
Mostefai, Hadj Ahmed;Meziani, Ferhat;Andriantsitohaina, Ramaroson
通讯作者：
Andriantsitohaina, Ramaroson
DOI：
10.1016/j.jbc.2021.100759
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
Lee AS
DOI：
10.1152/ajpheart.00903.2011
发表时间：
2012-01-01
影响因子：
4.8
作者：
Christians, Elisabeth S.;Benjamin, Ivor J.
通讯作者：
Benjamin, Ivor J.