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

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-03-15 DOI:10.1016/j.intimp.2025.114454
Guangtao Li , Bin Liu , Hongxia Yang , Dan Zhang , Shangguo Wang , Zehua Zhang , Zijian Zhao , Yanghe Zhang , Honglan Zhou , Yishu Wang
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Abstract

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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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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