Orphan receptor GPR153 facilitates vascular damage responses by modulating cAMP levels, YAP/TAZ signaling, and NF-κB activation

Jingchen Shao, Jeonghyeon Kwon, Tianpeng Wang, Stefan Günther, Lukas S. Tombor, Timothy Warwick, Zaib Shaheryar, Ralf P. Brandes, Stefanie Dimmeler, Jan Wenzel, Stefan Offermanns, Markus Schwaninger and Nina Wettschureck ()
Additional contact information
Jingchen Shao: Max Planck Institute for Heart and Lung Research
Jeonghyeon Kwon: Max Planck Institute for Heart and Lung Research
Tianpeng Wang: Max Planck Institute for Heart and Lung Research
Stefan Günther: Max Planck Institute for Heart and Lung Research
Lukas S. Tombor: Partner Site Rhine-Main
Timothy Warwick: Partner Site Rhine-Main
Zaib Shaheryar: University of Lübeck
Ralf P. Brandes: Partner Site Rhine-Main
Stefanie Dimmeler: Partner Site Rhine-Main
Jan Wenzel: University of Lübeck
Stefan Offermanns: Max Planck Institute for Heart and Lung Research
Markus Schwaninger: University of Lübeck
Nina Wettschureck: Max Planck Institute for Heart and Lung Research

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract Vascular cells express various G-protein-coupled receptors (GPCRs) with yet unknown function, among them orphan receptor GPR153. GPR153 was upregulated in smooth muscle cells (SMCs) in response to injury, and knockdown of GPR153 resulted in reduced proliferation and mildly altered differentiation in human SMCs. Mice with tamoxifen-inducible, SMC-specific GPR153 deficiency were partially protected against ligation-induced neointima formation, and their SMCs were characterized by reduced proliferation and dedifferentiation. Mechanistically, we show that GPR153 negatively regulates cellular cAMP levels, and thus the absence of GPR153 leads to an increase in CREB phosphorylation, reduced YAP/TAZ levels, and diminished NF-κB activation. Interestingly, a similar role of GPR153 was observed in endothelial cells (ECs), where loss of GPR153 resulted in reduced inflammatory gene expression and protected mice with EC-specific GPR153 deficiency in models of neuroinflammation and stroke. Taken together, orphan receptor GPR153 facilitates pro-inflammatory and pro-proliferative gene expression in ECs and SMCs by controlling cellular cAMP levels, thereby contributing to inflammation and vascular remodeling.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61057-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61057-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61057-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().