@article{ZHU2024, 
author = {Lin ZHU and Guilian XU and Pan XIE and Kanfu PENG},
title = {Role of Fgl2 in macrophage polarization during acute kidney injury in mice},
year = {2024},
journal = {Journal of Army Medical University},
volume = {46},
number = {13},
pages = {1467-1476},
keywords = {cisplatin, acute kidney injury, fibrinogen-like protein 2, macrophage},
url = {https://www.sciopen.com/article/10.16016/j.2097-0927.202401019},
doi = {10.16016/j.2097-0927.202401019},
abstract = {ObjectiveTo investigate the role of fibrinogen-like protein 2 (Fgl2) in macrophage polarization during cisplatin (Cis)-induced acute kidney injury (Cis-AKI).MethodsTwelve 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.ResultsCompared 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).ConclusionFgl2 gene knockout exacerbates Cis-AKI by promoting macrophage polarization towards the M1 phenotype.}
}