Berberine Acts on C/EBPβ/lncRNA Gas5/miR-18a-5p Loop to Decrease the Mitochondrial ROS Generation in HK-2 Cells

Berberine (BBR) has therapeutic effect on diabetic nephropathy (DN), but its molecular mechanism is not completely clear. The DN model was established to observe the therapeutic effect of BBR. The expression levels of lncRNA Gas5 were detected by PCR. The transcriptional regulation of CCAAT enhancer...

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Published inFrontiers in endocrinology (Lausanne) Vol. 12; p. 675834
Main Authors Xu, Jiang, Liu, Linqing, Gan, Lin, Hu, Yuanyuan, Xiang, Ping, Xing, Yan, Zhu, Jie, Ye, Shandong
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 30.08.2021
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ISSN1664-2392
1664-2392
DOI10.3389/fendo.2021.675834

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Summary:Berberine (BBR) has therapeutic effect on diabetic nephropathy (DN), but its molecular mechanism is not completely clear. The DN model was established to observe the therapeutic effect of BBR. The expression levels of lncRNA Gas5 were detected by PCR. The transcriptional regulation of CCAAT enhancer binding protein beta (C/EBPβ) on Gas5 was analyzed by chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and luciferase reporter gene assay. The targeted regulation between Gas5 and miR-18a-5p and between miR-18a-5p and C/EBPβ 3'-untranslated region (3'-UTR) was also analyzed. In HG environment, BBR decreased the mitochondrial reactive oxygen species (ROS) generation and activated the C/EBPβ expression in HK-2 cells; C/EBPβ could combine with the reaction element on the promoter of Gas5 to promote its expression. Gas5 also inhibited the miR-18a-5p expression as competing endogenous RNA (ceRNA) and reduce the negative regulatory effect of miR-18a-5p on C/EBPβ. BBR could activate C/EBPβ/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signal pathway, regulate mitochondrial energy metabolism, and inhibit ROS production and apoptosis by activating C/EBPβ/Gas5/miR-18a-5p positive feedback loop in HG environment. It also showed that BBR alleviated streptozotocin (STZ) induced renal injury in DN rats . This study suggested that BBR could regulate the mitochondrial ROS generation by activating the positive feedback loop of C/EBPβ/Gas5/miR-18a-5p.
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Edited by: Aida Martinez-Sanchez, Imperial College London, United Kingdom
This article was submitted to Diabetes: Molecular Mechanisms, a section of the journal Frontiers in Endocrinology
Reviewed by: Ming Yang, Central South University, China; Shikun Yang, The Third Xiangya Hospital of Central South University, China; Wang Yunjie, Yantai University, China
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2021.675834