Abstract: FR-PO0168
Tubular Cell-Derived Enolase 1 Promotes Inflammatory Macrophage Activation and AKI in Mice
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Gu, Mengru, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Li, Ying, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Cheng, Long, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Fu, Shiyu, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Dai, Chunsun, Center for Kidney Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Background
Enolase 1 (Eno1), a key glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate, is highly expressed in tubular cells. Previous studies have shown that tubular cells can secrete Eno1 following injury. However, the role and mechanisms of tubular cell-derived Eno1 in acute kidney injury (AKI) remain largely unknown.
Methods
Primary cultured tubular epithelial cells were treated with hydrogen peroxide or cisplatin to induce cellular injury. Bone marrow-derived macrophages (BMMs) were stimulated with LPS and/or conditioned medium from cultured tubular cells. Bilateral renal ischemia-reperfusion injury (BIRI) was performed in mice to establish an AKI model. A mouse model with proximal tubular cell ablation of APT2 was generated using the Cre-LoxP system.
Results
We first found that treatment with hydrogen peroxide or cisplatin induced Eno1 secretion in tubular cells via the TMED10-mediated unconventional protein secretion (THU) pathway. Furthermore, palmitoylation of Eno1 at cysteine 389 facilitated its binding to TMED10 and subsequent secretion. Ablation of APT2 or overexpression of DHHC21 in tubular cells resulted in increased Eno1 palmitoylation at cysteine 389 and secretion, whereas knockdown of DHHC21 reduced Eno1 palmitoylation and secretion. Additionally, purified Eno1 protein significantly promoted macrophage M1 polarization. Mechanistically, Eno1 bind to the extracellular domain of Toll-like receptor 2 (TLR2) on macrophages, stimulating NF-κB signaling activation and promoting M1 polarization. In the mouse model, ablation of APT2 in proximal tubular cells enhanced Eno1 secretion and exacerbated IRI-induced AKI.
Conclusion
This study demonstrates that tubular cell-derived Eno1 binds to TLR2 on macrophages, promoting NF-κB signaling pathway activation and macrophage M1 polarization, ultimately exacerbating AKI. Targeting Eno1 secretion may provide a novel strategy for intervening in AKI.
Funding
- Government Support – Non-U.S.