Role of Fgl2 in macrophage polarization during acute kidney injury in mice
10.16016/j.2097-0927.202401019
- VernacularTitle:Fgl2对小鼠急性肾损伤中巨噬细胞极化的作用
- Author:
Lin ZHU
1
;
Guilian XU
;
Pan XIE
;
Kanfu PENG
Author Information
1. 400038 重庆,陆军军医大学(第三军医大学)第一附属医院肾内科
- Keywords:
cisplatin;
acute kidney injury;
fibrinogen-like protein 2;
macrophage
- From:
Journal of Army Medical University
2024;46(13):1467-1476
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of fibrinogen-like protein 2(Fgl2)in macrophage polarization during cisplatin(Cis)-induced acute kidney injury(Cis-AKI).Methods Twelve male wild-type(Fgl2+/+)mice and 12 Fgl2 gene knockout(Fgl2)mice,aged 8～10 weeks and weighing 20～25 g,were selected,and then after being administered with a single intraperitoneal injection of either saline or Cis for 3 d,they were randomly divided into 4 groups(n=6):Fgl2+/+Saline group,Fgl2+/+Cis group,Fgl2 Saline group and Fgl2 Cis group.Kidney function indicators such as serum creatinine(Scr)and blood urea nitrogen(BUN)levels were measured 3 d later,and kidney injury was assessed by HE staining.Western blot analysis was performed to evaluate the expression of Fgl2 and kidney injury molecule 1(Kim-1)in the renal tissues.RT-qPCR was conducted to assess the expression levels of Fgl2,Kim-1,neutrophil gelatinase-associated lipocalin(NGAL),IL-6,IL-12p40,IL-1β,inducible nitric oxide synthase(iNOS)and TNF-α in the renal tissues.Immunohistochemical assay was employed to detect the expression of Fgl2 and macrophages(F4/80+)in the kidneys.Immunofluorescence staining was utilized to examine the expression of macrophages(F4/80+)and M1-type macrophages(F4/80+CD86+)in the renal tissues.Flow cytometry was employed to analyze the expression of macrophages(F4/80+)as well as M1-type macrophages(F4/80+MHC Ⅱ+)and M2-type macrophages(F4/80+CD206+)in the renal tissues.Results Compared with the Fgl2+/+Saline group,the Fgl2+/+Cis group exhibited a significant decline in renal function(P＜0.05),a notable increase in pathological score of renal tubular injury(P＜0.05),and an obvious upregulation of renal tissue Fgl2 expression(P＜0.05).Compared with the Fgl2+/+Cis group,the Fgl2 Cis group demonstrated a significant decline in renal function(P＜0.05),an elevation in the expression of renal injury-associated molecules Kim-1 and NGAL(P＜0.05),an increase in pathological score of renal tubular injury(P＜0.05),increase in macrophage infiltration(P＜0.05),and an upregulation in the expression of M1-type macrophage-related molecules IL-6,IL-1β,TNF-α and iNOS(P＜0.05),as well as obviously increase in the percentage of M1-type macrophages as indicated by flow cytometry(P＜0.05),while there was no significant change in the percentage of M2-type macrophages,and the proportion of M1-type macrophages was significantly higher than that of M2-type macrophages(P＜0.05).Conclusion Fgl2 gene knockout exacerbates Cis-AKI by promoting macrophage polarization towards the M1 phenotype.
