Effect of miR-532-3p on macrophage polarization in rats with chronic kidney disease through targeted inhibition of Notch1 signal pathway
10.3969/j.issn.1000-484X.2025.02.009
- VernacularTitle:miR-532-3p靶向抑制Notch1信号通路对慢性肾脏病大鼠巨噬细胞极化的影响
- Author:
Mingzhi XU
1
;
Na AN
1
;
Yafei BAI
1
;
Ruman CHEN
1
;
Jiqing HE
1
;
Chunli WANG
1
;
Yonghui QI
1
;
Mingjiao PAN
1
Author Information
1. 海南省人民医院·海南医学院附属海南医院血液净化中心,海口 570311
- Publication Type:Journal Article
- Keywords:
Chronic kidney disease;
Macrophage polarization;
miR-532-3p;
Notch1
- From:
Chinese Journal of Immunology
2025;41(2):310-314,319
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze effect of miR-532-3p on macrophage polarization in rats with chronic kidney disease(CKD)through targeted inhibition of Notch1 signal pathway.Methods:A total of 75 SD rats were divided into control group,CKD group,ago-NC group,ago-miR-532-3p group and FLI-06 group,except for control group,CKD models were constructed and corresponding plas-mids and inhibitors were injected,control group and CKD group were replaced with same amount of normal saline.Serum creatinine(Scr),blood urea nitrogen(BUN),TNF-α,IL-1β and IL-10 were measured by ELISA,HE staining and Masson staining were used to observe renal tissue pathology and renal fibrosis in rats,flow cytometry was used to detect CD11c+and CD206+of macrophages,miR-532-3p expression in rat kidney tissue was detected by qRT-PCR,Notch1 protein was detected by Western blot;target binding of miR-532-3p to Notch1 was determined by double luciferase reporter gene.Results:Structure of glomerulus,renal tubules and epithelial cells was complete,cell boundaries were clear,and cells were arranged neatly in control group;glomerular epithelial cell necrosis,mesangial matrix,glomerulosclerosis,inflammatory cell infiltration and renal fibrosis were increased in CKD group;compared with CKD group,damage degree of glomerulus and tubules,inflammatory infiltration cells and renal fibrosis degree in ago-miR-532-3p group and FLI-06 group were reduced;compared with control group,serum Scr,BUN,TNF-α,IL-1β,proportion of CD11c+,CD11c+/CD206+and Notch1 protein expression in macrophages of renal tissue were increased,serum IL-10 level,CD206+and miR-532-3p in renal tissue were decreased(P<0.05);compared with CKD group,serum Scr,BUN,TNF-α,IL-1β,proportion of CD11c+,CD11c+/CD206+and Notch1 protein expression in macrophages of renal tissue in ago-miR-532-3p group and FLI-06 group were decreased,serum IL-10 level,CD206+and miR-532-3p in renal tissue were increased(P<0.05);miR-532-3p targeted Notch1,and overexpression of miR-532-3p inhibited Notch1 protein expression.Conclusion:Promoting expression of miR-532-3p protects kidney tissue of CKD rats by inhibiting Notch1 pathway,which may be due to regulating polarization of macrophages.