Abstract: TH-PO0231
Targeting TRPM3 Channels Attenuates Renal Fibrosis by Influencing Maladaptive Repair State of Tubular Cells
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Liang, Hanzhi, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Lv, Haoran, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Wang, Le, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Liu, Qinghua, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Zhou, Yiming, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
Background
Maladaptive repair state of proximal tubular epithelial cells (PTECs) is increasingly recognized as a key driver of chronic kidney disease (CKD) progression and fibrosis. However, the upstream regulators controlling maladaptive repair state remain incompletely understood. Transient receptor potential melastatin 3 (TRPM3), a calcium-permeable ion channel, has been implicated in stress responses. This study aimed to investigate the function and contribution of TRPM3 channels in maladaptive repair PTECs and kidney fibrosis.
Methods
Public single-cell RNA sequencing datasets from multiple kidney injury models were analyzed to characterize TRPM3 expression during tubular injury and repair. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) in wild-type and Trpm3 knockout mice. Human kidney organoids and cultured tubular epithelial cells were treated with the TRPM3 agonist or inhibitor. Histological staining, immunofluorescence, Western blotting, and quantitative PCR were performed to evaluate tubular injury, fibrotic changes, and maladaptive repair phenotypes.
Results
Single-cell transcriptomic analysis revealed that TRPM3 was predominantly enriched in failed repair proximal tubular cells and progressively increased during kidney injury and fibrosis. TRPM3 expression showed strong association with maladaptive repair markers and profibrotic phenotypes. Genetic deletion of Trpm3 significantly attenuated tubular injury, collagen deposition, and fibrotic marker expression in UUO kidneys. In human kidney organoids and tubular epithelial cells, pharmacological activation of TRPM3 promoted maladaptive tubular phenotypes and profibrotic changes, whereas pharmacological inhibition of TRPM3 markedly alleviated these changes. Mechanistically, TRPM3 activation enhanced maladaptive repair programs and promoted profibrotic transcriptional responses in injured tubular epithelial cells.
Conclusion
TRPM3 promotes maladaptive tubular repair and renal fibrosis and may represent a potential therapeutic target for CKD progression, highlighting the therapeutic potential of targeting TRPM3 in chronic kidney injury and fibrosis.
Funding
- Government Support – Non-U.S.