Kidney Week

Abstract: TH-PO0659

Macrophage GPR30 Protects Against AKI Progression by Sustaining Peroxisome Proliferator-Activated Receptor γ (PPARγ)-Dependent Cholesterol Homeostasis

Session Information

• AKI: Mechanisms - Inflammation and Repair
  October 22, 2026 | Location: Exhibit Hall A, 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

Xiangchen Gu

• Quan, Jinwei, Shanghai Fourth People's Hospital, Shanghai, China

Jinwei Quan

• Wang, Chenxi, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China

Chenxi Wang

• Gu, Yaodong, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China

Yaodong Gu

• Cheng, Ye, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China

Ye Cheng

• Chen, Min, Shanghai University of Traditional Chinese Medicine Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China

Min Chen, MD

Background

Female patients often exhibit a lower incidence, reduced severity, and lower mortality of AKI than male patients, suggesting a potential protective role of estrogen signaling in AKI. Recent studies have shown that estrogen and estrogen receptor signaling can protect renal tubular epithelial cells from injury, in part by suppressing ferroptosis. However, whether membrane estrogen receptors regulate AKI progression remains unclear. Our previous work demonstrated that macrophage GPR30 ameliorates renal fibrosis in unilateral ureteral obstruction. In the present study, we aimed to investigate the role of macrophage GPR30 in AKI progression.

Methods

Macrophage-specific Gpr30 knockout mice were generated using Lyz2-Cre and Gpr30fl/fl mice and subjected to cisplatin- or ischemia-reperfusion–induced AKI with wild-type littermates. Renal function, histological injury, injury markers, and inflammatory cytokines were assessed. Single-cell RNA sequencing and high-definition spatial transcriptomics were used to identify macrophage-associated pathways. In vitro knockdown and activation assays examined the GPR30–PPARγ–ApoB receptor axis in macrophage cholesterol homeostasis, and in vivo GPR30 agonist treatment tested therapeutic protection against cisplatin-induced AKI.

Results

We successfully generated macrophage-specific Gpr30 knockout mice and confirmed efficient Gpr30 deletion in macrophages. Compared with wild-type controls, Gpr30 conditional knockout mice subjected to cisplatin injection or ischemia-reperfusion injury exhibited higher serum creatinine levels and more severe tubular injury on histological examination. qPCR analysis further showed increased expression of inflammatory cytokines and tubular injury markers in the kidneys of Gpr30 conditional knockout mice. Single-cell RNA sequencing and high-definition spatial transcriptomics further suggested that GPR30 may regulate the ApoB–ApoB receptor axis during AKI progression. In vitro, GPR30 interacted with PPARγ and modulated the expression of ApoBR, ABCA1 and ABCG1, thereby regulating macrophage cholesterol homeostasis. Pharmacological activation of GPR30 attenuated cisplatin-induced AKI.

Conclusion

Macrophage GPR30 plays a protective role in AKI progression by regulating cholesterol homeostasis. These findings identify macrophage GPR30 as a potential therapeutic target for AKI.

Acknowledgment

This study was supported by the National Natural Science Foundation of China (Grant No. 82474175, to X. G.)

Funding

• Government Support – Non-U.S.