Abstract: TH-PO1142
Colchicine Attenuates Kidney Injury via Modulation of the NLRP3 Inflammasome 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
- Ryu, Jaejin, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
- Heo, Ga Young, Division of Nephrology, Department of Internal Medicine, Korea University, Seoul, Korea (the Republic of)
- Kim, Gyu ri, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
- Cho, Yoojin, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
- Nam, Boyoung, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
- Park, Jung Tak, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
- Yoo, Tae-Hyun, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
- Kang, Shin-Wook, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
- Han, Seung Hyeok, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
Background
Chronic kidney disease (CKD) is a progressive loss of kidney function driven by inflammation and fibrosis, ultimately leading to kidney failure. Chronic inflammation plays a crucial role in CKD progression. Colchicine, a well-known anti-inflammatory drug, has emerged as a therapeutic option in various inflammatory diseases. However, its role in CKD remains unclear. This study aims to investigate the reno-protective effects of colchicine in an experimental CKD model and its potential role in modulating the NOD-like receptor, pyrin domain containing protein 3 (NLRP3) inflammasome pathway.
Methods
A CKD animal model was established in C57BL/6 mice by feeding a 2% adenine-containing diet. Colchicine (0.3 mg/kg/day) or saline was administered intraperitoneally for 4 weeks. RNA sequencing of kidney tissue was performed to capture molecular signatures associated with the therapeutic mechanism of colchicine in CKD. In vitro, renal tubular epithelial cells (RTECs) were treated with transforming growth factor-β (TGF-β, 10 ng/ml) and bone marrow-derived macrophages (BMDMs) were exposed to p-cresol sulfate (PCS, 0.5 mM). Colchicine (0.1 μM for RTECs and 1.0 μM for BMDMs) was administered to evaluate its protective effects. Fibrosis markers and NLRP3 inflammasome pathway were examined in kidney tissue, RTECs and BMDMs.
Results
Adenine-fed CKD mice exhibited systemic inflammation, as evidenced by increased circulating levels of inflammatory cytokines including Interleukin-1β, Interleukin-6, and Tumor Necrosis Factor-α. Colchicine treatment significantly reduced these inflammatory markers. In the kidney tissues of adenine-fed mice, prominent fibrotic change and macrophage infiltration were observed, both of which were significantly attenuated by colchicine treatment. These improvements were accompanied by reduced albuminuria and improved kidney function. Mechanistically, colchicine directly inhibited the interaction between NLRP3 and ASC in TGF-β-treatd RTECs and PCS-treated BMDMs, resulting in decreased NLRP inflammasome assembly, as demonstrated by oligomerization cross-liking assay and proximity ligation assay.
Conclusion
This study demonstrated that colchicine can attenuate kidney injury and fibrosis in adenine-induced CKD mice via inhibiting NLRP3 inflammasome assembly and activation.