Autoantibodies targeting AT1-and ETa-receptors link endothelial proliferation and coagulation via ets-1 transcription factor

Rusan Catar*, Melanie Herse-Naether, Nan Zhu, Philine Wagner, Oskar Wischnewski, Angelika Kusch, Julian Kamhieh-Milz, Andreas Eisenreich, Ursula Rauch, Björn Hegner, Harald Heidecke, Angela Kill, Gabriela Riemekasten, Gunnar Kleinau, Patrick Scheerer, Duska Dragun, Aurelie Philippe*

*Corresponding author for this work
5 Citations (Scopus)


Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (AT1 R) and endothelin-1 type A receptors (ETA R) on downstream signaling events and endothelial cell proliferation. SRC-IgG triggered endothelial cell proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway and subsequent activation of the E26 transformation-specific-1 transcription factor (Ets-1). Either AT1 R or ETA R receptor inhibitors/shRNA abrogated endothelial proliferation, confirming receptor activation and Ets-1 signaling involvement. Binding of Ets-1 to the tissue factor (TF) promoter exclusively induced TF. In addition, TF inhibition prevented endothelial cell proliferation. Thus, our data revealed a thus far unknown link between SRC-IgG-induced intracellular signaling, endothelial cell proliferation and active coagulation in the context of obliterative vasculopathy and SRC. Patients’ autoantibodies and their molecular effectors represent new therapeutic targets to address severe vascular complications in SSc.

Original languageEnglish
Article number244
JournalInternational Journal of Molecular Sciences
Issue number1
Publication statusPublished - 01.01.2022

Research Areas and Centers

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


Dive into the research topics of 'Autoantibodies targeting AT1-and ETa-receptors link endothelial proliferation and coagulation via ets-1 transcription factor'. Together they form a unique fingerprint.

Cite this