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

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

作者地址："[Lin, Ziyue; Lv, Dan; Liao, Xiaohui; Sun, Yan; Zhang, Zheng] Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing, Peoples R China; [Lin, Ziyue; Lv, Dan; Wu, Tianhui; Wu, Keqian; Sun, Yan; Zhang, Zheng] Chongqing Med Univ, Dept Cell Biol & Genet, Chongqing, Peoples R China; [Peng, Rui] Chongqing Med Univ, Dept Bioinformat, Chongqing, Peoples R China; [Liu, Handeng] Chongqing Med Univ, Ctr Teaching & Learning, Chongqing, Peoples R China"

通信作者："Sun, Y; Zhang, Z (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing, Peoples R China.; Sun, Y; Zhang, Z (通讯作者)，Chongqing Med Univ, Dept Cell Biol & Genet, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001067397700001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：diabetic kidney disease; CircUBXN7; IGF2BP2; macrophage infiltration; epithelial-mesenchymal transition; tubulointerstitial fibrosis

摘要："IntroductionInflammatory cell infiltration is a novel hallmark of diabetic kidney disease (DKD), in part, by activated macrophages. Macrophage-to-tubular epithelial cell communication may play an important role in renal fibrosis. Circular RNAs (circRNAs) have been reported in the pathogenesis of various human diseases involving macrophages activation, including DKD. However, the exact mechanism of circRNAs in macrophage infiltration and renal fibrosis of DKD remains obscure.MethodsIn 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.ResultsWe 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.ConclusionCircUBXN7 is highly expressed in DKD patients may provide the potential biomarker and therapeutic target for DKD."

基金机构："National Natural Science Foundations of China [82270876, 81970702]; Science and Technology Research Program of Chongqing Municipal Education Commission [CSTB2022NSCQ-MSX0126]; CQMU program for youth innovation in future medicine [w0173]"

基金资助正文："This study was funded by the National Natural Science Foundations of China (No. 82270876 and 81970702), the Science and Technology Research Program of Chongqing Municipal Education Commission (CSTB2022NSCQ-MSX0126) and CQMU program for youth innovation in future medicine (w0173)."