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

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

doi:10.1016/j.clim.2025.110454

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

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

^*Corresponding author for this work

Abstract

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.

Original language	English
Article number	110454
Journal	Clinical Immunology
Volume	273
Pages (from-to)	110454
ISSN	1521-6616
DOIs	https://doi.org/10.1016/j.clim.2025.110454
Publication status	Published - 04.2025

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

2.22-18 Rheumatology
2.21-05 Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.clim.2025.110454

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Wang, P., Wu, D., Gong, Z., Adu-Gyamfi, M., Kamhieh-Milz, J., da Fonseca, D. L. M., Sürücü, G., Ashraf, M. I., Heidecke, H., Sikorska, D., Cabral-Marques, O., Moll, G., Riemekasten, G., Witowski, J., & Catar, R. (2025). Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis. Clinical Immunology, 273, 110454. Article 110454. https://doi.org/10.1016/j.clim.2025.110454

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title = "Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis",

abstract = "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.",

author = "Pinchao Wang and Dashan Wu and Zexian Gong and Michael Adu-Gyamfi and Julian Kamhieh-Milz and {da Fonseca}, {Dennyson Leandro Mathias} and G{\"u}listan S{\"u}r{\"u}c{\"u} and Ashraf, {Muhammad I.} and Harald Heidecke and Dorota Sikorska and Otavio Cabral-Marques and Guido Moll and Gabriela Riemekasten and Janusz Witowski and Rusan Catar",

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Wang, P, Wu, D, Gong, Z, Adu-Gyamfi, M, Kamhieh-Milz, J, da Fonseca, DLM, Sürücü, G, Ashraf, MI, Heidecke, H, Sikorska, D, Cabral-Marques, O, Moll, G, Riemekasten, G, Witowski, J & Catar, R 2025, 'Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis', Clinical Immunology, vol. 273, 110454, pp. 110454. https://doi.org/10.1016/j.clim.2025.110454

TY - JOUR

T1 - Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis

AU - Wang, Pinchao

AU - Wu, Dashan

AU - Gong, Zexian

AU - Adu-Gyamfi, Michael

AU - Kamhieh-Milz, Julian

AU - da Fonseca, Dennyson Leandro Mathias

AU - Sürücü, Gülistan

AU - Ashraf, Muhammad I.

AU - Heidecke, Harald

AU - Sikorska, Dorota

AU - Cabral-Marques, Otavio

AU - Moll, Guido

AU - Riemekasten, Gabriela

AU - Witowski, Janusz

AU - Catar, Rusan

PY - 2025/4

Y1 - 2025/4

N2 - 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.

AB - 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.

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

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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