Emodin inhibits M1 macrophage activation that related to acute and chronic kidney injury through EGFR/MAPK pathway

• Published in: Functional & integrative genomics 2024-08, Vol.24 (4), p.131, Article 131
• Main Authors: Xiong, Weijian, Tang, Jing, Yu, Hangxing, Luo, Yan, Yu, Minghuan, Li, Ying
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Acute Kidney Injury - genetics; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Animal Genetics and Genomics; Animals; Biochemistry; Bioinformatics; Biomedical and Life Sciences; CD86 antigen; Cell activation; Cell Biology; Cell culture; Cell viability; Cytokines; Cytokines - genetics; Cytokines - metabolism; Emodin; Emodin - pharmacology; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Gene expression; Homeostasis; IL-1β; Immune response; Inflammation; Interleukin 6; Kidney diseases; Life Sciences; Lipopolysaccharides; Macrophage Activation - drug effects; Macrophages; Macrophages - drug effects; Macrophages - metabolism; MAP kinase; MAP Kinase Signaling System - drug effects; Mice; Microbial Genetics and Genomics; mRNA; Pharmacology; Plant Genetics and Genomics; Plasmids; Polarization; RAW 264.7 Cells; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; Signal transduction; Surface markers; Tumor necrosis factor-α
• ISSN: 1438-793X; 1438-7948; 1438-7948
• DOI: 10.1007/s10142-024-01407-x

Background Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages. Methods Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1β, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD. Results There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1β and TNF-α ( p