PMID- 36405683
OWN - NLM
STAT- MEDLINE
DCOM- 20221122
LR  - 20221122
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Pathophysiological conditions induced by SARS-CoV-2 infection reduce ACE2 
      expression in the lung.
PG  - 1028613
LID - 10.3389/fimmu.2022.1028613 [doi]
LID - 1028613
AB  - SARS-CoV-2 infection causes a variety of physiological responses in the lung, and 
      understanding how the expression of SARS-CoV-2 receptor, angiotensin-converting 
      enzyme 2 (ACE2), and its proteolytic activator, transmembrane serine protease 2 
      (TMPRSS2), are affected in patients with underlying disease such as interstitial 
      pneumonia will be important in considering COVID-19 progression. We examined the 
      expression of ACE2 and TMPRSS2 in an induced usual interstitial pneumonia (iUIP) 
      mouse model and patients with IPF as well as the changes in whole-lung ACE2 and 
      TMPRSS2 expression under physiological conditions caused by viral infection. 
      Histopathological and biochemical characteristics were analyzed using human 
      specimens from patients with IPF and precision-cut lung slices (PCLS) from iUIP 
      mouse model showing UIP with honeycombing and severe fibrosis after non-specific 
      interstitial pneumonia. ACE2 expression decreased with acute lung inflammation 
      and increased in the abnormal lung epithelium of the iUIP mouse model. ACE2 is 
      also expressed in metaplastic epithelial cells. Poly(I:C), interferons, and 
      cytokines associated with fibrosis decreased ACE2 expression in PCLS in the iUIP 
      model. Hypoxia also decreases ACE2 via HIF1alpha in PCLS. Antifibrotic agent, 
      nintedanib attenuates ACE2 expression in invasive epithelial cells. Patients with 
      IPF are at a higher risk of SARS-CoV-2 infection due to the high expression of 
      ACE2. However, ACE2 and TMPRSS2 expression is decreased by immune intermediaries, 
      including interferons and cytokines that are associated with viral infection and 
      upon administration of antifibrotic agents, suggesting that most of the viral 
      infection-induced pathophysiological responses aid the development of resistance 
      against SARS-CoV-2 infection.
CI  - Copyright (c) 2022 Miura, Ohkubo, Nakano, Bourke and Kanazawa.
FAU - Miura, Yoko
AU  - Miura Y
AD  - Department of Neurodevelopmental Disorder Genetics, Nagoya City University 
      Graduate School of Medical Sciences, Nagoya, Japan.
FAU - Ohkubo, Hirotsugu
AU  - Ohkubo H
AD  - Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City 
      University Graduate School of Medical Sciences, Nagoya, Japan.
FAU - Nakano, Akiko
AU  - Nakano A
AD  - Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City 
      University Graduate School of Medical Sciences, Nagoya, Japan.
FAU - Bourke, Jane E
AU  - Bourke JE
AD  - Department of Pharmacology, Biomedicine Discovery Institute, Monash University, 
      Clayton, VA, Australia.
FAU - Kanazawa, Satoshi
AU  - Kanazawa S
AD  - Department of Neurodevelopmental Disorder Genetics, Nagoya City University 
      Graduate School of Medical Sciences, Nagoya, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221104
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - 0 (Cytokines)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Angiotensin-Converting Enzyme 2/genetics
MH  - *COVID-19
MH  - Peptidyl-Dipeptidase A/metabolism
MH  - SARS-CoV-2
MH  - Lung/pathology
MH  - *Lung Diseases/pathology
MH  - *Idiopathic Pulmonary Fibrosis/pathology
MH  - Cytokines
MH  - Interferons
MH  - Fibrosis
PMC - PMC9673245
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - angiotensin converting enzyme 2 (ACE2)
OT  - idiopathic pulmonary fibrosis (IPF)
OT  - precision-cut lung slices (PCLS)
OT  - serine 2 (TMPRSS2)
OT  - transmembrane protease
COIS- The authors declare that the research was conducted in the absence of any 
      commercial of financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/22 06:00
MHDA- 2022/11/23 06:00
PMCR- 2022/11/04
CRDT- 2022/11/21 04:02
PHST- 2022/08/26 00:00 [received]
PHST- 2022/10/14 00:00 [accepted]
PHST- 2022/11/21 04:02 [entrez]
PHST- 2022/11/22 06:00 [pubmed]
PHST- 2022/11/23 06:00 [medline]
PHST- 2022/11/04 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1028613 [doi]
PST - epublish
SO  - Front Immunol. 2022 Nov 4;13:1028613. doi: 10.3389/fimmu.2022.1028613. 
      eCollection 2022.