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Pleural Mesothelial Cells Modulate the Inflammatory/Profibrotic Response During SARS-CoV-2 Infection.
Matusali, Giulia; Trionfetti, Flavia; Bordoni, Veronica; Nardacci, Roberta; Falasca, Laura; Colombo, Daniele; Terri, Michela; Montaldo, Claudia; Castilletti, Concetta; Mariotti, Davide; Del Nonno, Franca; Capobianchi, Maria Rosaria; Agrati, Chiara; Tripodi, Marco; Strippoli, Raffaele.
  • Matusali G; Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
  • Trionfetti F; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Bordoni V; Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
  • Nardacci R; Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy.
  • Falasca L; Laboratory of Electron Microscopy, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.
  • Colombo D; UniCamillus-Saint Camillus International University of Health and Medical Sciences, Rome, Italy.
  • Terri M; Laboratory of Electron Microscopy, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.
  • Montaldo C; Laboratory of Electron Microscopy, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.
  • Castilletti C; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Mariotti D; Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
  • Del Nonno F; Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
  • Capobianchi MR; Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
  • Agrati C; Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases "L. Spallanzani" IRCCS, Rome, Italy.
  • Tripodi M; Laboratory of Electron Microscopy, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.
  • Strippoli R; Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
Front Mol Biosci ; 8: 752616, 2021.
Article in English | MEDLINE | ID: covidwho-1572298
ABSTRACT
Although lung fibrosis has a major impact in COVID-19 disease, its pathogenesis is incompletely understood. In particular, no direct evidence of pleura implication in COVID-19-related fibrotic damage has been reported so far. In this study, the expression of epithelial cytokeratins and Wilms tumor 1 (WT1), specific markers of mesothelial cells (MCs), was analyzed in COVID-19 and unrelated pleura autoptic samples. SARS-CoV-2 replication was analyzed by RT-PCR and confocal microscopy in MeT5A, a pleura MC line. SARS-CoV-2 receptors were analyzed by RT-PCR and western blot. Inflammatory cytokines from the supernatants of SARS-CoV-2-infected MeT5A cells were analysed by Luminex and ELLA assays. Immunohistochemistry of COVID-19 pleura patients highlighted disruption of pleura monolayer and fibrosis of the sub-mesothelial stroma, with the presence of MCs with fibroblastoid morphology in the sub-mesothelial stroma, but no evidence of direct infection in vivo. Interestingly, we found evidence of ACE2 expression in MCs from pleura of COVID-19 patients. In vitro analysis shown that MeT5A cells expressed ACE2, TMPRSS2, ADAM17 and NRP1, plasma membrane receptors implicated in SARS-CoV-2 cell entry and infectivity. Moreover, MeT5A cells sustained SARS-CoV-2 replication and productive infection. Infected MeT5A cells produced interferons, inflammatory cytokines and metalloproteases. Overall, our data highlight the potential role of pleura MCs as promoters of the fibrotic reaction and regulators of the immune response upon SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Front Mol Biosci Year: 2021 Document Type: Article Affiliation country: Fmolb.2021.752616

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Front Mol Biosci Year: 2021 Document Type: Article Affiliation country: Fmolb.2021.752616