Role of JMJD3 in drug-associated acute kidney injury in mice
10.3760/cma.j.cn131073.20210915.00320
- VernacularTitle:JMJD3在小鼠药物相关性急性肾损伤中的作用
- Author:
Wenqiang YU
1
;
Benquan LIU
;
Hua LIANG
;
Jiayi NIE
;
Chaoqun ZHONG
Author Information
1. 佛山市第一人民医院麻醉科，佛山 528000
- Keywords:
Jumonji domain-containing histone demethylases;
Acute kidney injury;
Apoptosis;
Inflammation
- From:
Chinese Journal of Anesthesiology
2022;42(3):342-346
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of histone demethylase (JMJD3) in drug-induced acute kidney injury (AKI) in mice.Methods:Twenty-four male C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups ( n =6 each) using a random number table method: control group (C group), AKI group, a specific JMJD3 inhibitor GSKJ4+ control group (GSKJ4 group), and GSKJ4-AKI group.Folic acid 250 mg/kg was injected intraperitoneally to develop AKI model.GSKJ4 20 mg/kg was intraperitoneally injected at 1 h before developing AKI model in GSKJ4-AKI group and at the corresponding time point in GSKJ4 group.Blood samples were collected at 72 h after development of AKI model for determination of serum BUN and Cr concentrations.The animals were then sacrificed and renal tissues were collected for microscopic examination of histopathological morphology (using HE and PAS staining) and for determination of cell apoptosis (by TUNEL) and expression of JMJD3, Bax and cleaved caspase-3 (by Western blot), the number of JMJD3, myeloperoxidase (MPO), F4/80 and CD3 positive cells, expression of cleaved caspase-3 and Bax, and expression of IL-1β, IL-6, TNF-α and monocyte chemotactic protein 1 (MCP-1) mRNA (by reverse transcription polymerase chain reaction). The damage to the renal tubules was scored. Results:Compared with C group, the serum BUN and Cr concentrations and renal tubular damage score were significantly increased, the number of JMJD3, myeloperoxidase (MPO), F4/80 and CD3 + positive cells was increased, the number of apoptotic cells was increased, and the expression of Bax, cleaved caspase-3, JMJD3 and IL-1β, TNF-α, IL-6 and MCP-1 mRNA was up-regulated in AKI group ( P<0.05), and no significant change was found in the parameters mentioned above in GSKJ4 group ( P>0.05). Compared with AKI group, the serum BUN and Cr concentrations and renal tubular damage score were significantly decreased, the number of JMJD3, myeloperoxidase (MPO), F4/80 and CD3 positive cells was decreased, the number of apoptotic cells was decreased, and the expression of Bax, cleaved caspase-3, JMJD3, and IL-1β, TNF-α, IL-6 and MCP-1 mRNA was down-regulated in GSKJ4-AKI group ( P<0.05). Conclusions:The mechanism of drug-associated AKI may be related to up-regulation of JMJD3 expression and thus induces cell apoptosis and inflammatory responses in mice.
