Objective: To explore whether overexpression of NR4A1 can alleviate lupus nephritis (LN). Methods: A mouse model of LN was constructed by intraperitoneal injection of 0.5 mL pristane

divided into saline control group (SC)

pristane control group (PC)

vector control group (VC) and overexpressed NR4A1 group. At the end of 20thweek

the monocytes overexpressed NR4A1 were injected into the tail vein. The diameter of ankles was measured at the end of 28thweek. Renal pathological sections were stained with HE staining and semi-quantitative scores were used to assess renal pathological damage. Serum TNF-α and anti-ds-DNA concentrations were measured by ELISA. The expression of Bcl-2 and NR4A1 in the spleen was detected by real-time PCR. Results: The results showed that compared with the SC group

LN-related activity indicators in the PC group were significantly increased

but the ankle joint diameter[4.69 (4.26

5.13) mm

P=0.000]

the anti-ds-DNA antibody concentration [(173.11±25.49) ng/mL

P=0.000]

renal pathology score[2.78 (2.68

2.81)

P=0.000]

and the expression of NR4A1 (0.40±0.09

P=0.008) was significantly reduced. Compared with the PC and VC groups

the NR4A1 group LN activity indicators were significantly improved

the ankle joint diameter[3.80 (3.44

4.20) mm

PPC=0.002

PVC=0.033]

the concentration of anti-ds-DNA antibody [(51.92±10.91) ng/mL

PPC=0.008

PVC=0.025]

renal pathology score[1.39 (1.30

1.49)

PPC=0.002

PVC=0.018].ELISA results showed that the concentration of TNF-α in the NR4A1 group [(542.86±108.28) pg/mL]was significantly lower than that of the PC group [(1 779.00±358.40) pg/mL

P=0.008]and the VC group [(1 759.71±280.27) pg/mL

P=0.010].Real-time PCR results showed that the expression of Bcl-2 gene in the NR4A1 group (1.92±0.58) was significantly higher than that of the PC group (0.48±0.20

P=0.000). Conclusion: Overexpression of NR4A1 alleviates the symptoms of LN and reduces LN activity indicators in LN mice

which may involve the interaction among NR4A1

TNF-α and Bcl-2.