Expression of SARS-CoV-2 Entry Factors in Human Alveolar Type II Cells in Aging and Emphysema.

Expression of SARS-CoV-2 Entry Factors in Human Alveolar Type II Cells in Aging and Emphysema.
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DOI:
10.3390/biomedicines9070779
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发表时间:
2021-07-06
期刊:
影响因子:
4.7
通讯作者:
Kosmider B
Kosmider B
中科院分区:
工程技术3区
文献类型:
--
作者:
Lin CR;Bahmed K;Simborio H;Hayek H;Bolla S;Marchetti N;Criner GJ;Kosmider B

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肺泡II型(ATII)细胞增殖并恢复受损的上皮。已经描述了SARS-CoV-2感染引起肺部弥漫性肺泡损伤。然而,促进ATII细胞中的病毒感染的宿主因子并不为人所知。我们分别用RT-PCR和Western blotting检测了从年轻和老年非吸烟者、吸烟者和戒烟者中分离的ATII细胞中SARS-CoV-2相关基因和蛋白的表达。细胞也从肺气肿患者的肺移植物中获得。ACE 2已被确定为SARS-CoV-2的受体,我们发现年轻和老年吸烟者以及肺气肿患者的ACE 2水平显着增加。病毒进入依赖于TMPRSS 2蛋白酶活性,并且在老年吸烟者和戒烟者以及肺气肿患者中检测到较高的表达。与非吸烟者相比,ACE 2和TMPRSS 2 mRNA水平在这种疾病中更高。CD 209 L作为SARS-CoV-2的受体,我们发现从吸烟者和肺气肿患者中获得的ATII细胞中的水平增加。此外,我们的数据表明miR 142对CD 209 L的调节。内质网应激检测ATII细胞在这种疾病。我们的研究结果表明,在老年人,吸烟者和肺气肿患者的ATII细胞中SARS-CoV-2进入因子的上调可能会促进感染。
Alveolar type II (ATII) cells proliferate and restore the injured epithelium. It has been described that SARS-CoV-2 infection causes diffuse alveolar damage in the lungs. However, host factors facilitating virus infection in ATII cells are not well known. We determined the SARS-CoV-2-related genes and protein expression using RT-PCR and Western blotting, respectively, in ATII cells isolated from young and elderly non-smokers, smokers, and ex-smokers. Cells were also obtained from lung transplants of emphysema patients. ACE2 has been identified as the receptor for SARS-CoV-2, and we found significantly increased levels in young and elderly smokers and emphysema patients. The viral entry depends on TMPRSS2 protease activity, and a higher expression was detected in elderly smokers and ex-smokers and emphysema patients. Both ACE2 and TMPRSS2 mRNA levels were higher in this disease in comparison with non-smokers. CD209L serves as a receptor for SARS-CoV-2, and we found increased levels in ATII cells obtained from smokers and in emphysema patients. Also, our data suggest CD209L regulation by miR142. Endoplasmic reticulum stress was detected in ATII cells in this disease. Our results suggest that upregulation of SARS-CoV-2 entry factors in ATII cells in aging, smokers, and emphysema patients may facilitate infection.
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