In well-differentiated primary human bronchial epithelial cells, TGF-β1 and TGF-β2 induce expression of furin
| Autor: | Jennifer A. Mitchel, Michael O'Sullivan, Jin-Ah Park, Maureen McGill, Phyllis J. Kanki, Chimwemwe Mwase |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
TGF-β
0301 basic medicine Pulmonary and Respiratory Medicine 2019-20 coronavirus outbreak Coronavirus disease 2019 (COVID-19) Physiology viruses Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ACE2 Gene Expression Bronchi Disease Models Biological TMPRSS2 Transforming Growth Factor beta1 Transforming Growth Factor beta2 03 medical and health sciences 0302 clinical medicine Physiology (medical) Humans RNA Messenger Pandemics Furin Cells Cultured Rapid Report Host Microbial Interactions biology SARS-CoV-2 Serine Endopeptidases COVID-19 Cell Differentiation Epithelial Cells Cell Biology Virus Internalization respiratory tract diseases Well differentiated 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research Angiotensin-Converting Enzyme 2 Disease Susceptibility Transforming growth factor |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology Am J Physiol Lung Cell Mol Physiol |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | The COVID-19 pandemic is an ongoing threat to public health. Since the identification of COVID-19, the disease caused by SARS-CoV-2, no drugs have been developed to specifically target SARS-CoV-2. To develop effective and safe treatment options, a better understanding of cellular mechanisms underlying SARS-CoV-2 infection is required. To fill this knowledge gap, researchers require reliable experimental systems that express the host factor proteins necessary for the cellular entry of SARS-CoV-2. These proteins include the viral receptor, angiotensin-converting enzyme 2 (ACE2), and the proteases, transmembrane serine protease 2 (TMPRSS2) and furin. A number of studies have reported cell-type-specific expression of the genes encoding these molecules. However, less is known about the protein expression of these molecules. We assessed the suitability of primary human bronchial epithelial (HBE) cells maintained in an air-liquid interface (ALI) as an experimental system for studying SARS-CoV-2 infection in vitro. During cellular differentiation, we measured the expression of ACE2, TMPRSS2, and furin over progressive ALI days by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence staining. We also explored the effect of the fibrotic cytokine TGF-β on the expression of these proteins in well-differentiated HBE cells. Like ACE2, TMPRSS2 and furin proteins are localized in differentiated ciliated cells, as confirmed by immunofluorescence staining. These data suggest that well-differentiated HBE cells maintained in ALI are a reliable in vitro system for investigating cellular mechanisms of SARS-CoV-2 infection. We further identified that the profibrotic mediators, TGF-β1 and TGF-β2, increase the expression of furin, which is a protease required for the cellular entry of SARS-CoV-2. |
| Databáze: | OpenAIRE |
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