Abstract: TH-PO1158
Protein Arginine Methyltransferase 5 Promotes Renal Fibrosis via Activation of the Epidermal Growth Factor Receptor Signaling Pathway
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Yu, Chao, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Shen, Fengchen, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yao, Liyuan, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Du, Xinyu, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Wang, Yanjin, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yu, Jianjun, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Yan, Zhipeng, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Zhuang, Shougang, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Background
Protein Arginine Methyltransferase 5 (PRMT5) is a key enzyme responsible for the symmetric dimethylation of arginine residues on both histone and non-histone proteins, playing a significant role in various cellular processes. However, its involvement in renal fibrosis has yet to be explored.
Methods
Renal tubular deficient mice lacking PRMT5 and EPZ015938, a selective inhibitor of PRMT5, were utilized to investigate the role of PRMT5 in renal fibrosis across three murine models: unilateral ureteral obstruction (UUO), unilateral ischemia/reperfusion injury (UIRI), and 5/6 nephrectomy (SNx). Immunostaining was performed to assess the renal expression of PRMT5 and macrophage infiltration. Additionally, immunoblot analysis was conducted to evaluate the expression and/or phosphorylation of proteins associated with renal fibrosis in both kidney tissues and cultured renal proximal tubular cells (RTPCs).
Results
PRMT5 exhibited high expression levels in renal tubular cells across all three models, as well as in human kidney samples and cultured RTPCs. The deletion of PRMT5 from renal tubules or treatment with EPZ015938 significantly reduced renal fibrosis along with the expression of several extracellular matrix (ECM) proteins, including fibronectin, collagen type I, and alpha-smooth muscle actin. Transfection with siRNA targeting PRMT5 or direct treatment also led to decreased ECM protein levels in cultured RTPCs. Furthermore, both genetic knockout and pharmacological inhibition of PRMT5 resulted in diminished epithelial-mesenchymal transition both in vivo and in vitro. Notably, these interventions inhibited the phosphorylation of epidermal growth factor receptor (EGFR) as well as several intracellular signaling pathways implicated in the progression of renal fibrosis—specifically Smad3, ERK1/2, AKT, NF-kB, and STAT3.
Conclusion
These findings indicate that PRMT5 plays a critical role in the development of renal fibrosis through the activation of multiple profibrotic signaling pathways.
Funding
- Government Support – Non-U.S.