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The orphan receptor GPRC5B modulates inflammatory and fibrotic pathways in cardiac fibroblasts and mice hearts
- Source :
- Biochemical and biophysical research communications. 514(4)
- Publication Year :
- 2019
-
Abstract
- Inflammation is a major driver of cardiac remodeling. Cardiac fibroblasts play an integral role in cardiac inflammation, fibrosis and remodeling. The orphan G-protein-coupled-receptor 5B of family C (GPRC5B) has recently been shown to have pro-inflammatory effects in adipocytes via the NFκB-signaling-pathway. Here, we investigated whether GPRC5B is involved in myocardial inflammation and fibrosis. Using neonatal rat cardiac fibroblasts (NRCF) we show that the transcription and the expression of endogenous GPRC5B is induced by stimulation with TNFα and LPS as well as through cyclic mechanical stretch, while the principle pro-fibrotic factor TGFβ has no effect on the GPRC5B expression. Furthermore, we demonstrate that adenoviral overexpression and siRNA-mediated knockdown of GPRC5B in NRCF significantly alters the transcription level of the pro-inflammatory and pro-fibrotic cytokines TNFα, IL-1β, IL-6 and MCP-1, and extracellular matrix-degrading MMP-9 in vitro. Additionally, in adult GPRC5B-transgenic mice the protein expression of collagen-1A1 is decreased and the production of MMP-9 is increased, indicating remodeling of the extracellular matrix in vivo. Our data show that GPRC5B is up-regulated by inflammatory signals and mechanical stress in NRCF, while GPRC5B modulates the inflammatory response of cardiac fibroblasts and the degradation of extracellular matrix-proteins in the mice heart. Thus, our findings are the first to report a novel role of the orphan receptor GPRC5B in fibroblast-driven myocardial inflammation and cardiac remodeling.
- Subjects :
- 0301 basic medicine
Biophysics
Inflammation
Mice, Transgenic
Biochemistry
Receptors, G-Protein-Coupled
Extracellular matrix
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
medicine
Extracellular
Animals
Humans
Molecular Biology
Cells, Cultured
G protein-coupled receptor
Orphan receptor
Gene knockdown
business.industry
Myocardium
Heart
Cell Biology
Fibroblasts
medicine.disease
Cell biology
Mice, Inbred C57BL
030104 developmental biology
030220 oncology & carcinogenesis
Tumor necrosis factor alpha
medicine.symptom
business
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 514
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....796fca2b97b0376ae2420480bb5db99a