CircUBXN7 promotes macrophage infiltration and renal fibrosis associated with the IGF2BP2-dependent SP1 mRNA stability in diabetic kidney disease

CircUBXN7 促进糖尿病肾病中 IGF2BP2 依赖性 SP1 mRNA 稳定性相关的巨噬细胞浸润和肾纤维化

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作者:Ziyue Lin, Dan Lv, Xiaohui Liao, Rui Peng, Handeng Liu, Tianhui Wu, Keqian Wu, Yan Sun, Zheng Zhang

Conclusion

CircUBXN7 is highly expressed in DKD patients may provide the potential biomarker and therapeutic target for DKD.

Methods

In our study, a novel circRNA circUBXN7 was identified in DKD patients using microarray. The function of circUBXN7 in vitro and in vivo was investigated by qRT-PCR, western blot, and immunofluorescence. Finally, a dual-luciferase reporter assay, ChIP, RNA pull-down, RNA immunoprecipitation and rescue experiments were performed to investigate the mechanism of circUBXN7.

Results

We demonstrated that the expression of circUBXN7 was significantly upregulated in the plasma of DKD patients and correlated with renal function, which might serve as an independent biomarker for DKD patients. According to investigations, ectopic expression of circUBXN7 promoted macrophage activation, EMT and fibrosis in vitro, and increased macrophage infiltration, EMT, fibrosis and proteinuria in vivo. Mechanistically, circUBXN7 was transcriptionally upregulated by transcription factor SP1 and could reciprocally promote SP1 mRNA stability and activation via directly binding to the m6A-reader IGF2BP2 in DKD.

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