Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis

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Wang, Pinchao ; Wu, Dashan ; Gong, Zexian ; Adu-Gyamfi, Michael ; Kamhieh-Milz, Julian ; da Fonseca, Dennyson Leandro Mathias ; Sueruecue, Guelistan ; Ashraf, Muhammad I. ; Heidecke, Harald ; Sikorska, Dorota ; Cabral-Marques, Otavio ; Moll, Guido ; Riemekasten, Gabriela ; Witowski, Janusz ; Catar, Rusan

• Tipo de documento: Artigo Científico
• Fonte: Clinical Immunology; v. 273, p. 10-pg., 2025-02-20.

Resumo

Here, we investigate how autoantibodies against G protein-coupled receptors (GPCRs) on endothelial cells, which are present in patients with scleroderma renal crisis (SRC) impact on endothelin-1 (ET-1) production in human microvascular endothelial cells (HMECs). To this end, serum IgG fraction was isolated from SRC patients and applied to HMECs in culture. Compared to cells treated with either plain control medium or serum IgG from healthy individuals, exposure of HMECs to SRC-IgG resulted in a time- and concentration-dependent increase in ET-1 expression and release. This effect could be blocked by the protease activated receptor 1 (PAR1) inhibitor and mimicked by thrombin, the PAR1 activator. Transcription factor C-FOS/AP-1 and tissue factor (TF) were identified as mediators of these responses. Thus, it can be concluded that serum IgG fraction from SRC patients stimulates endothelial cells to produce ET-1, acting through PAR1 in cooperation with TF. (AU)

• Processo FAPESP: 20/07069-0 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com COVID-19
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/01688-0 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 18/18886-9 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores