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SARS-CoV-2-related peptides induce endothelial-to-mesenchymal transition in endothelial capillary cells derived from different body districts: focus on membrane (M) protein.
Baldassarro, Vito Antonio; Alastra, Giuseppe; Cescatti, Maura; Quadalti, Corinne; Lorenzini, Luca; Giardino, Luciana; Calzà, Laura.
Afiliación
  • Baldassarro VA; Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
  • Alastra G; Interdepartmental Centre for Industrial Research in Health Sciences and Technology ICIR-HST, University of Bologna, Bologna, Italy.
  • Cescatti M; Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
  • Quadalti C; IRET Foundation, Ozzano Emilia, Italy.
  • Lorenzini L; Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy.
  • Giardino L; Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
  • Calzà L; Interdepartmental Centre for Industrial Research in Health Sciences and Technology ICIR-HST, University of Bologna, Bologna, Italy.
Cell Tissue Res ; 397(3): 241-262, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38953987
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19, may lead to multiple organ dysfunctions and long-term complications. The induction of microvascular dysfunction is regarded as a main player in these pathological processes. To investigate the possible impact of SARS-CoV-2-induced endothelial-to-mesenchymal transition (EndMT) on fibrosis in "long-COVID" syndrome, we used primary cultures of human microvascular cells derived from the lungs, as the main infection target, compared to cells derived from different organs (dermis, heart, kidney, liver, brain) and to the HUVEC cell line. To mimic the virus action, we used mixed SARS-CoV-2 peptide fragments (PepTivator®) of spike (S), nucleocapsid (N), and membrane (M) proteins. TGFß2 and cytokine mix (IL-1ß, IL-6, TNFα) were used as positive controls. The percentage of cells positive to mesenchymal and endothelial markers was quantified by high content screening. We demonstrated that S+N+M mix induces irreversible EndMT in all analyzed endothelial cells via the TGFß pathway, as demonstrated by ApoA1 treatment. We then tested the contribution of single peptides in lung and brain cells, demonstrating that EndMT is triggered by M peptide. This was confirmed by transfection experiment, inducing the endogenous expression of the glycoprotein M in lung-derived cells. In conclusion, we demonstrated that SARS-CoV-2 peptides induce EndMT in microvascular endothelial cells from multiple body districts. The different peptides play different roles in the induction and maintenance of the virus-mediated effects, which are organ-specific. These results corroborate the hypothesis of the SARS-CoV-2-mediated microvascular damage underlying the multiple organ dysfunctions and the long-COVID syndrome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Endoteliales / Transición Epitelial-Mesenquimal / SARS-CoV-2 / COVID-19 Límite: Humans Idioma: En Revista: Cell Tissue Res Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Endoteliales / Transición Epitelial-Mesenquimal / SARS-CoV-2 / COVID-19 Límite: Humans Idioma: En Revista: Cell Tissue Res Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Alemania