Pachymic acid regulates inflammatory response in rats with chronic glomerulonephritis via the MCP-1/CCR2 signaling pathway
XIE Yu-duan1, LI Han-lian1, HAN Yan1, YU Ting2, LI Wei3
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1. Department of Laboratory, Wang Jing Hospital of CACMS, Beijing 100102, China; 2. Department of Laboratory, Wuhan Mental Health Center, Wuhan 430012, China; 3. Internal Medicine, Wang Jing Hospital of CACMS, Beijing 100102, China
The aim of this study is to investigate the impact of pachymic acid (PA) on inflammatory response in rats with chronic glomerulonephritis (CGN) by regulating monocyte chemoattractant protein 1(MCP-1)/CC chemokine receptor 2(CCR2) signaling pathway. Ten SD rats were randomly selected as the control group, and the rest were injected with cationic bovine serum albumin (C-BSA) to establish the CGN model. Successfully modeled rats were randomly divided into CGN group, PA group (10 mg/kg PA), GW0742 group (0.3 mg/kg GW0742), and PA+GW0742 group (10 mg/kg PA+0.3 mg/kg GW0742), with 10 rats in each group. 24-h urine protein, serum creatinine(Scr), blood urea nitrogen (BUN), antioxidant index and inflammatory index were detected with the corresponding commercial kits. The pathological injury of renal tissue was detected by H-E staining, and the levels of IgG and C3 in glomerulus were detected by immunofluorescence staining. The mRNA expressions of MCP-1 and CCR2 were detected by qRT-PCR. Western blotting was used to detect the expressions of MCP-1/CCR2 signaling pathway related proteins. The results showed that rats in the control group had normal renal tissue whereas in the CGN group, both capillary rings and Bowman sacs were thickened, and degeneration of renal tubular epithelial cells and infiltration of inflammatory cells were observed. Compared to those of the control group, the levels of 24-h urine protein, Scr, and BUN, the levels of IL-1β and TNF-α, degree of renal tissue injury, fluorescence relative intensity of IgG and C3, and the mRNA and the protein levels of MCP-1 and CCR2 in the CGN group significantly increased(P<0.05), while the levels of superoxide dismutase (SOD)and glutathione (GSH) significantly decreased (P<0.05). PA was shown to improve the above indicators, while GW0742 induced opposite changes of these indicators compared to those of the PA group. GW0742 attenuated the improvement effect of PA on inflammatory response in CGN rats. This study suggests that PA may improve the inflammatory response of CGN rats by down-regulating MCP-1/CCR2 signaling pathway.
XIE Yu-duan, LI Han-lian, HAN Yan, YU Ting, LI Wei.
Pachymic acid regulates inflammatory response in rats with chronic glomerulonephritis via the MCP-1/CCR2 signaling pathway. Current Immunology. 2025, 45(1): 37-42