Omega-3 polyunsaturated fatty acids alleviate renal fibrosis in chronic kidney disease by reducing macrophage activation and infiltration through the JAG1-NOTCH1/2 pathway

纤维化 医学 肾脏疾病 渗透(HVAC) 多不饱和脂肪酸 病理 巨噬细胞 内科学 化学 生物化学 脂肪酸 物理 体外 热力学
作者
Guangtao Li,Bin Liu,Hongxia Yang,Dan Zhang,Shangguo Wang,Zehua Zhang,Zijian Zhao,Yanghe Zhang,Honglan Zhou,Yishu Wang
出处
期刊:International Immunopharmacology [Elsevier BV]
卷期号:152: 114454-114454
标识
DOI:10.1016/j.intimp.2025.114454
摘要

In recent years, the global incidence of chronic kidney disease (CKD) has been rising. As CKD progresses, it frequently involves inflammatory cell infiltration, contributing to renal fibrosis. Current research indicates that abnormalities in lipid metabolism play a role in this fibrotic process. However, the specific effects of various dietary fatty acids on renal inflammation and fibrosis remains largely unexplored. Our study demonstrates that dietary intake of omega-3 polyunsaturated fatty acids can inhibit macrophage activation and infiltration in a mouse model of unilateral ureteral obstruction (UUO), thus reducing the severity of renal fibrosis. Omega-3 polyunsaturated fatty acids, particularly α-linolenic acid (α-LA), mitigate damage to HK-2 cells and macrophages by targeting the JAG1-NOTCH1/2 pathway and by downregulating the expression of the chemokine MCP-1 and its receptor CCR2. This modulation attenuates macrophage activation and infiltration, reducing the inflammatory response. Furthermore, these fatty acids inhibit fibroblast chemotaxis, reduce fibroblast activation, and mitigate the deposition of extracellular matrix (ECM), thus slowing the progression of renal fibrosis. Our findings underscore the protective effects of omega-3 polyunsaturated fatty acids, such as α-LA, in preventing injury, inhibiting macrophage activation, and alleviating fibrosis. These results suggests that adjusting the dietary balance of fatty acids may offer a promising strategy to enhance the efficacy of CKD treatment.
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