Abstract: SA-PO0120
Macrophage GPR30 Protects Against AKI by Maintaining Cholesterol Efflux and Limiting Lipid-Driven Inflammation
Session Information
- AKI: Mechanisms - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Gu, Xiangchen, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- Wang, Chenxi, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- Cheng, Ye, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- Gu, Yaodong, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- Chen, Min, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
Background
Acute kidney injury (AKI) is an escalating global health burden, with macrophages driving both inflammation and injury progression. While their immune functions are well established, macrophage behavior is increasingly recognized to be shaped by metabolic reprogramming, particularly lipid metabolism. Yet, the role of cholesterol metabolism in renal macrophages remains largely unclear. We previously showed that GPR30 in macrophages suppresses M1 polarization and fibrosis. Here, we demonstrate that GPR30 preserves cholesterol homeostasis and restrains lipid-induced inflammation in AKI.
Methods
We generated myeloid-specific Gpr30 knockout (MKO) mice by crossing Lyz2-Cre with Gpr30fl/fl mice. MKO and WT littermates were subjected to three AKI models: cisplatin-induced, ischemia reperfusion injury, and aristolochic acid I induced AKI to CKD transition. Renal function, histopathology, immune cell infiltration, and fibrotic markers were assessed. Sc-RNA sequencing was performed on cisplatin-injured kidneys to explore cell-type specific responses and intracellular signaling, especially lipid-related communication. BMDMs were stimulated with oxLDL, with or without GPR30 activation, to assess cholesterol efflux and intracellular lipid accumulation. GPR30 activation in vivo was also examined.
Results
Gpr30 deficient mice exhibited significantly impaired renal function, worsened tubular injury, and elevated expression of inflammatory and fibrotic markers across all AKI models. scRNA-seq further revealed enhanced macrophage activation and tubular injuries in MKO kidneys. CellChat2 analysis identified enhanced lipid-related ligand–receptor signaling between proximal tubular cells and macrophages. In vitro, Gpr30-deficient macrophages exhibited impaired cholesterol efflux, characterized by reduced ABCA1/ABCG1 expression, and increased oxLDL accumulation. Pharmacological activation of GPR30 restored cholesterol homeostasis in vitro and attenuated acute renal injury in vivo.
Conclusion
Our study reveals GPR30 as a key regulator of macrophage cholesterol efflux and lipid–immune crosstalk during AKI. By preserving lipid homeostasis, GPR30 limits inflammation and protects against kidney injury. These findings uncover a previously unrecognized role of cholesterol metabolism in renal macrophages and highlight GPR30 as a promising therapeutic target in AKI.
Funding
- Government Support – Non-U.S.