Abstract: FR-PO1217
ALOX5 Regulates Renal Fibrosis Through Modulation of Matrix Remodeling and Inflammatory Responses
Session Information
- CKD: Mechanisms, AKI, and Beyond - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Moon, Youngyoon, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Joo, Yoosun, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Lim, Hyun Ji, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Choi, Hana, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Lee, Tae Hoon, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Jung, Su Woong, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Lee, Sang ho, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Moon, Ju young, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
Background
Renal fibrosis, a common pathological feature of Chronic Kidney Disease (CKD), exhibits excessive extracellular matrix accumulation and inflammatory cell infiltration. 5-lipoxygenase (ALOX5), a key enzyme in leukotriene biosynthesis, plays crucial roles in inflammatory cell recruitment and inflammatory responses. While ALOX5-mediated LTB4 production is known to regulate inflammatory cascade and immune cell recruitment, its specific contribution to collagen deposition and matrix remodeling in renal fibrosis remains unclear.
Methods
We investigated the role of ALOX5 in renal fibrosis using TGFβ-stimulated HKC8 cells (human proximal tubule cell) with pharmacological ALOX5 inhibition. We analyzed the expression of fibrotic markers and pro-inflammatory cytokines using Western blot and qPCR. We further examined matrix metalloproteinases (MMPs), total soluble collagen expression, and collagen turnover through molecular and biochemical analyses. To evaluate immune cell recruitment, we established co-culture systems with immune cells.
Results
ALOX5 inhibition effectively suppressed TGFβ-induced increases in alpha-smooth muscle actin (α-SMA) and kidney injury molecule-1 (KIM-1) expression in HKC8 cells. ALOX5 pathway modulation significantly affected TGFβ-induced collagen expression, attenuating the expression of total soluble collagen. Collagen composition and turnover were also affected, evidenced by the changes of the TGF-β-induced collagen I to III ratio. The ratio showed reversal at different time points. Mechanistically, ALOX5 inhibition restored the TGFβ-suppressed expression and enzymatic activities of key collagenases (MMP1, MMP3, and MMP13), maintaining appropriate collagen turnover. Furthermore, ALOX5 pathway blockade reduced IL-6, IL-1β levels and immune cell infiltration in co-culture experiments, demonstrating its regulatory role in matrix remodeling and inflammatory responses.
Conclusion
ALOX5 serves as a critical mediator in renal fibrosis by regulating collagen deposition and inflammatory responses. ALOX5 pathway modulation affects multiple aspects of fibrotic progression: regulation of collagen turnover, inflammatory cytokine production, and immune cell recruitment. These results establish ALOX5 as a potential therapeutic target in renal fibrosis, particularly through its role in matrix remodeling.