miRNA-155-5P靶向调控SOCS1调节JAK2/STAT3信号通路对狼疮性肾炎肾脏损伤的影响

doi:10.3969/j.issn.1006-5725.2025.09.003

Abstract

Abstract:

Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1 （SOCS1） in regulating the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in renal injury associated with lupus nephritis （LN）. Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups （n = 6 per group）： the model group， the antagomir NC group， the miR-155-5p antagomir group， the miR-155-5p antagomir + shRNA control group， and the miR-155-5p antagomir + SOCS1 shRNA group. The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir， antagomir NC， SOCS1 shRNA， or shRNA control. Additionally， six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline. Serum blood urea nitrogen （BUN） and creatinine （Scr） levels， renal histopathological changes， and the expression levels of miR-155-5p， SOCS1， phosphorylated JAK2 （p-JAK2）， and phosphorylated STAT3 （p-STAT3） in renal tissues were evaluated. Results Compared with the normal group， the model group exhibited significantly elevated levels of BUN， Scr， miR-155-5p， p-JAK2， and p-STAT3 proteins in the kidneys （P < 0.01）， while the expression level of SOCS1 was markedly reduced （P < 0.01）. Compared with both the model group and the antagomir NC group， the miR-155-5p antagomir group showed decreased levels of BUN， Scr， miR-155-5p， p-JAK2， and p-STAT3 proteins （P < 0.01）， along with a significant increase in SOCS1 expression （P < 0.01）. Similarly， compared with the miR-155-5p antagomir group and the miR-155-5p antagomir + shRNA control group， the miR-155-5p antagomir + SOCS1 shRNA group demonstrated significantly higher levels of BUN， Scr， miR-155-5p， p-JAK2， and p-STAT3 proteins （P < 0.01）， while SOCS1 expression was notably decreased （P < 0.01）. Renal pathology analysis revealed that， compared to the normal group， the model group exhibited glomerular atrophy， extensive infiltration of inflammatory cells in the renal tubulointerstitial region， and partial renal tubular necrosis. In contrast， the miR-155-5p antagomir group showed marked improvements in glomerular atrophy， tubular necrosis， and inflammatory cell infiltration compared with the model group and antagomir NC group. Furthermore， compared with the miR-155-5p antagomir group and the miR-155-5p antagomir + shRNA control group， the miR-155-5p antagomir + SOCS1 shRNA group exhibited more severe glomerular atrophy， tubular necrosis， and inflammatory cell infiltration. Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1， potentially through the activation of the JAK2/STAT3 signaling pathway.

Key words: lupus nephritis, miR-155-5p, suppressor of cytokine signaling 1, JAK2/STAT3 signaling pathway

CLC Number:

R285.5

Aitao LIN,Zhimin HUANG,Zhiying ZHANG,Tingna FU,Liangxi LU,Xiaoyu LIU,Yini JIANG,Leilei ZHAO,Jinyu. WU. MiRNA-155-5p aggravates renal injury in lupus nephritis by targeting OCS1 to regulate the JAK2/STAT3 signaling pathway[J]. The Journal of Practical Medicine, 2025, 41(9): 1285-1292.

Figures/Tables 7

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References 35

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组别	BUN/（mmol/L）	SCr/（μmol/L）
正常组	2.812 ± 0.859	8.971 ± 2.009
模型组	12.40 ± 1.949^#	62.651 ± 5.976^#)
抑制对照组	12.91 ± 1.746	60.647 ± 7.187
miR-155-5p抑制组	8.062 ± 1.171^△	37.541 ± 6.662^△
抑制miR-155-5p+干扰对照组	8.462 ± 1.299^△	41.533 ± 7.920^△
抑制miR-155-5p+SOCS1干扰对照组	11.74 ± 1.634^▲?	58.028 ± 7.580^▲?
F值	39.396	58.836
P值	< 0.001	< 0.001

组别		miR-155-5p
正常组		1.023 ± 0.129
模型组		6.671 ± 0.877^#
抑制对照组		6.849 ± 0.674
miR-155-5p抑制组		2.852 ± 0.408^△
抑制miR-155-5p + 干扰对照组		3.064 ± 0.288^△
抑制miR-155-5p + SOCS1干扰对照组		4.767 ± 0.298^▲?
F值		60.822
P值		< 0.001

组别		SOCS1
正常组		0.746 ± 0.063
模型组		0.202 ± 0.035^#
抑制对照组		0.248 ± 0.052
miR-155-5p抑制组		0.515 ± 0.071^△
抑制miR-155-5p + 干扰对照组		0.628 ± 0.032^△
抑制miR-155-5p + SOCS1干扰对照组		0.372 ± 0.027^▲?
F值		56.921
P值		< 0.001

组别	p-JAK2	p-STAT3
正常组	0.152 ± 0.058	0.278 ± 0.091
模型组	1.045 ± 0.036^#	1.362 ± 0.097^#
抑制对照组	1.149 ± 0.027	1.390 ± 0.112
miR-155-5p抑制组	0.431 ± 0.091^△	0.566 ± 0.125^△
抑制miR-155-5p + 干扰对照组	0.485 ± 0.085^△	0.685 ± 0.289^△
抑制miR-155-5p + SOCS1干扰对照组	0.913 ± 0.116^▲?	1.112 ± 0.150^▲?
F值	82.403	54.329
P值	< 0.001	< 0.001

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MiRNA-155-5p aggravates renal injury in lupus nephritis by targeting OCS1 to regulate the JAK2/STAT3 signaling pathway

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