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September 2022 Cell-Type-Specific Effects of the Ovarian Cancer G-Protein Coupled Receptor (OGR1) on Inflammation and Fibrosis; Potential Implications for Idiopathic Pulmonary Fibrosis "Idiopathic pulmonary fibrosis (IPF) is a disease characterized by irreversible lung scarring. The pathophysiology is not fully understood, but the working hypothesis postulates that a combination of epithelial injury and myofibroblast differentiation drives progressive pulmonary fibrosis. We previously demonstrated that a reduction in extracellular pH activates latent TGF-β1, and that TGF-β1 then drives its own activation, creating a feed-forward mechanism that propagates myofibroblast differentiation. Given the important roles of extracellular pH in the progression of pulmonary fibrosis, we sought to identify whether pH mediates other cellular phenotypes independent of TGF-β1. Proton-sensing G-protein coupled receptors are activated by acidic environments, but their role in fibrosis has not been studied. Here, we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68) has dual roles in both promoting and mitigating pulmonary fibrosis. We demonstrate that OGR1 protein expression is significantly reduced in lung tissue from patients with IPF and that TGF-β1 decreases OGR1 expression. In fibroblasts, OGR1 inhibits myofibroblast differentiation and does not contribute to inflammation. However, in epithelial cells, OGR1 promotes epithelial to mesenchymal transition (EMT) and inflammation. We then demonstrate that sub-cellular localization and alternative signaling pathways may be responsible for the differential effect of OGR1 in each cell type. Our results suggest that strategies to selectively target OGR1 expression may represent a novel therapeutic strategy for pulmonary fibrosis." Read more at the source #DrGPCR #GPCR #IndustryNews

Oncology and Immunology Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2

DRD1 is exempt from TGFβ-mediated antifibrotic GPCR landscape tampering in lung fibroblasts. βHB inhibits

myofibroblast marker α-smooth muscle actin (αSMA), the profibrotic factor transforming growth factor β1 (TGFβ1 GPR176 expression was unaffected by TGFβ1 stimulation in rat renal fibroblast NRK-49 cells, whereas knockdown of Gpr176 by siRNA reduced TGFβ1-induced expression of αSMA, fibronectin, and collagen as well as Smad2 Hironobu Ishimaru, Kazuhito Tsuboi Tags Fibroblast , Fibrosis , Gpr176 , Myofibroblast , Orphan GPCR , TGFβ1

Oncology and Immunology Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 Transforming growth factor-β (TGFβ) is essential for alveologenesis and lung repair, and the G protein α subunits Gαq and Gα11 (Gαq/11) transmit mechanical and chemical signals to activate TGFβ in epithelial , but was independent of integrins, suggesting an isoform-specific role for TGFβ2 in this model. Tags Alveologenesis , Cyclical mechanical stretch , GPCR , Gαq/11 , Lung development , TGFβ .

Comparative analysis of the occupancy of Histone H3 Lysine 4 methylation in the cells treated with TGFβ Our study has compared the genes showing H3K4me3 occupancy in response to both TGFβ and IFNγ. Several genes were found to be shared between the TGFβ and IFNγ. DAVID Functional enrichment analysis in the TGFβ and IFNγ dataset revealed association of genes with activity, GPCR activity, TGFβ binding activity.