Abstract: FR-PO962
The Protective Role of GPER1 Against Renal Fibrosis
Session Information
- CKD: Pathobiology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Gu, Xiangchen, Department of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xie, Lin, Department of Nephrology, Yueyang Hospital of Integrated Traditional And Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Chen, Min, Department of Nephrology, Yueyang Hospital of Integrated Traditional And Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Wang, Yi, Department of Nephrology, Yueyang Hospital of Integrated Traditional And Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Xie, Jingyuan, Department of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
Male patients have a higher prevalence of CKD and increased rates of ESRD than those observed in female patients. Many factors are believed to be involved in this phenomenon. Whether GPER1(G protein-coupled estrogen receptor1), a de-novo estrogen receptor, plays a protective role against renal fibrosis remains unclear.
Methods
Using CRISPR/Cas9 gene-editing technique, we generated Gper1 global knockout mice. We subjected the mice to Aristolochic acid(AA) and Folic acid(FA) injection. We further analyzed the differentially expressed genes by bulk RNA-sequencing. We also cultured primary tubular epithelial cells from wild-type and Gper1-/- mice and treated the cells with TGFβ1. Finally, we treated AA-injected and FA-injected mice with a GPER1 agonist.
Results
In both AA and FA injection models, Gper1 knockout mice exhibited more severe renal fibrosis, increased inflammation infiltration, and decreased fatty acid oxidation, compared to wild-type mice. Bulk RNA sequencing also indicated a down-regulation of fatty acid oxidation and upregulation of inflammation in Gper1-/- renal tissues. In primary cell culture, TGFβ1-treated Gper1-/- TECs showed a reduction in the fatty acid oxidation pathway. Further, GPER1 agonist ameliorated renal fibrosis in AA-injected and FA-injected mouse models.
Conclusion
These results suggest that GPER1 may play a protective role against renal fibrosis through the fatty acid oxidation pathway. Activation of GPER1 expression may provide a new therapeutic target for CKD treatment.
Funding
- Government Support – Non-U.S.