2025-07-07 マックス・プランク研究所
Smooth muscle cells under a fluorescence microscope: If smooth muscle cells lack the GPR153 receptor (right), they divide significantly less than when GPR 153 is present. This can be seen in the white-coloured cell nuclei. The smooth muscle cells are coloured green. Cell nuclei that have not divided are shown in blue. © MPI for Heart and Lung Research
<関連情報>
- https://www.mpg.de/25128433/protein-switch-in-blood-vessels-exacerbates-damage-in-vascular-diseases
- https://www.nature.com/articles/s41467-025-61057-w
オーファン受容体GPR153は、cAMPレベル、YAP/TAZシグナル伝達、NF-κB活性化を調節することで血管損傷反応を促進する 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 & Nina Wettschureck
Nature Communications Published:07 July 2025
DOI:https://doi.org/10.1038/s41467-025-61057-w
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.
