Abstract: FR-PO1044
GPER1 Plays a Protective Role Against AKI to CKD Transition
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Gu, Xiangchen, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
- Xie, Lin, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
- Chen, Min, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai, Shanghai, China
- Wang, Yi, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai, Shanghai, China
- Xie, Jingyuan, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, 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. GPER1, a de novo estrogen receptor, has been shown to play an important role in the renal fibrosis process. Whether GPER1 is protective against AKI to CKD transition and its main mechanism 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) injections to mimic AKI to CKD transition. We treated AA-injected and FA-injected mice with a GPER1 agonist(G-1). We also cultured primary tubular epithelial cells(TECs) from wild-type and Gper1-/- mice and treated the primary cells and NRK-49F cell lines with TGFβ1 and oleic acid with or without G-1 administration.
Results
In both AA and FA injection models, Gper1 knockout mice exhibited more severe renal fibrosis, increased inflammation infiltration, decreased fatty acid oxidation, and activated PI3K/AKT pathway compared to wild-type mice. GPER1 agonist attenuated renal fibrosis and improved fatty acid oxidation in AA-injected and FA-injected mice models, respectively. In vitro study, TGFβ1-treated Gper1-/- TECs showed a reduction in fatty acid oxidation and ATP synthesis. GPER1 activation restored fatty acid oxidation and ATP synthesis, which were suppressed by TGFβ1 and oleic acid in primary PTECs and NRK-49F.
Conclusion
These results suggest that GPER1 may play a protective role against AKI to CKD transition through the fatty acid oxidation pathway. Activation of GPER1 expression may provide a new therapeutic target for AKI to CKD transition.
Funding
- Government Support – Non-U.S.