GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression DOI Creative Commons

Yasuo Okamoto,

Keisuke Kitakaze, Yasuhiro Takenouchi

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(7), P. 119798 - 119798

Published: July 22, 2024

Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets current antifibrotic drugs, no drug has yet been approved stop fibrosis progression. Herein, we aimed identify GPCRs with profibrotic effects. In gene expression analysis mouse lungs induced fibrosis, eight were identified, showing a >2-fold increase mRNA after induction. Among them, focused on Gpr176 owing its significant correlation myofibroblast marker α-smooth muscle actin (αSMA), factor transforming growth β1 (TGFβ1), and collagen human lung database. Similar model, increased was also observed other organs affected including kidney, liver, heart, suggesting role across various organs. Furthermore, fibroblasts abundantly expressed compared alveolar epithelial cells, endothelial macrophages fibrotic lung. GPR176 unaffected TGFβ1 stimulation rat renal fibroblast NRK-49 whereas knockdown siRNA reduced TGFβ1-induced αSMA, fibronectin, as well Smad2 phosphorylation. This suggested that regulates activation. Consequently, acts manner, inhibiting activity could potentially prevent differentiation improve fibrosis. Developing inverse agonist or allosteric modulator promising therapeutic approach for

Language: Английский

Screening of Regulatory mRNAs and miRNAs that Suppress Staphylococcus aureus Proliferation via Macrophage Ferroptosis DOI
Lili Wang, Jiajia Bao,

Danyang Yang

et al.

Current Microbiology, Journal Year: 2025, Volume and Issue: 82(4)

Published: Feb. 11, 2025

Language: Английский

Citations

0
GPR176 enhances the epithelial-mesenchymal transition in gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway DOI Creative Commons

Guang-Chuan Mu,

Kaiyan Li, Chen Hu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Gastric cancer is characterized by a high incidence and unfavorable prognosis. The exploration of novel molecular markers deeper understanding their mechanisms action hold the potential to offer fresh insights into gastric treatment. Leveraging TCGA-STAD GSE66254 datasets, this study conducted an analysis on relationship between GPR176 clinical pathological features. Furthermore, it was validated in patients from First Affiliated Hospital Guangxi Medical University. Cell migration invasion capabilities were evaluated through Transwell scratch assays. Western blot performed detect impact PI3K/AKT/mTOR signaling pathway. Nude mouse tumorigenesis experiments validate tumor growth in vivo. exhibited higher expression levels tissues, associated with poor prognosis cancer. Significant downregulation suppressed invasive migratory cells, concomitant inhibition PI3K EMT pathways. However, phenotypic changes induced its inhibitory effects could be reversed overexpression PIP5K1A. findings cell experiments, demonstrating that growth, while promoted growth. Similarly, after downregulation, pathways cells significantly inhibited, whereas upregulation led substantial activation. In conclusion, emerged as newly identified prognostic marker study. may promote activating

Language: Английский

Citations

0
GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression DOI Creative Commons

Yasuo Okamoto,

Keisuke Kitakaze, Yasuhiro Takenouchi

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(7), P. 119798 - 119798

Published: July 22, 2024

Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets current antifibrotic drugs, no drug has yet been approved stop fibrosis progression. Herein, we aimed identify GPCRs with profibrotic effects. In gene expression analysis mouse lungs induced fibrosis, eight were identified, showing a >2-fold increase mRNA after induction. Among them, focused on Gpr176 owing its significant correlation myofibroblast marker α-smooth muscle actin (αSMA), factor transforming growth β1 (TGFβ1), and collagen human lung database. Similar model, increased was also observed other organs affected including kidney, liver, heart, suggesting role across various organs. Furthermore, fibroblasts abundantly expressed compared alveolar epithelial cells, endothelial macrophages fibrotic lung. GPR176 unaffected TGFβ1 stimulation rat renal fibroblast NRK-49 whereas knockdown siRNA reduced TGFβ1-induced αSMA, fibronectin, as well Smad2 phosphorylation. This suggested that regulates activation. Consequently, acts manner, inhibiting activity could potentially prevent differentiation improve fibrosis. Developing inverse agonist or allosteric modulator promising therapeutic approach for

Language: Английский

Citations

1