LncRNA ZEB1-AS1 inhibits renal fibrosis in diabetic nephropathy by regulating the miR-217/MAFB axis

Song, Yan; Miao, Chang; Wang, Jianwen

doi:10.1039/c9ra05602e

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…The present results manifested that HG-treated HCFs showed repressed ZEB1-AS1 expression, increased cell viability, promoted cell migration, and augmented levels of collagen I, collagen III, fibronectin and α-SMA, whereas these trends were negated after overexpression of ZEB1-AS1. It is consistent that the decreases in fibronectin, α-SMA, collagen I and IV protein levels, induced by ZEB1-AS1 overexpression, are observed in HG-induced human kidney-2 cells and diabetic mice 9 . ZEB1-AS1 is underexpressed in kidney tissues of patients with diabetic nephropathy, and ZEB1-AS1 overexpression inhibits HG-triggered fibrogenesis 8 .…”

Section: Discussionsupporting

confidence: 83%

“…LncRNAs show aberrant expression patterns in diabetic cardiac tissues, and modulation of specific lncRNA expression levels causes pathophysiological changes in DCM 7 . LncRNA zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) inhibits high glucose (HG)-induced fibrogenesis and renal fibrosis in diabetic nephropathy 8,9 . Emerging evidence has shown that lncRNAs play the role of competing endogenous RNAs (ceRNAs) for microRNAs (miRNAs), and modulate their target gene expression in various diseases 10 .…”

Section: Introductionmentioning

confidence: 99%

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Long non‐coding ribonucleic acid zinc finger E‐box binding homeobox 1 antisense RNA 1 regulates myocardial fibrosis in diabetes through the Hippo–Yes‐associated protein signaling pathway

Lyu

Chen

et al. 2023

J of Diabetes Invest

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Aims/Introduction Fibrosis is the principle reason for heart failure in diabetes. Regarding the involvement of long non‐coding ribonucleic acid zinc finger E‐box binding homeobox 1 antisense 1 (ZEB1‐AS1) in diabetic myocardial fibrosis, we explored its specific mechanism. Materials and Methods Human cardiac fibroblasts (HCF) were treated with high glucose (HG) and manipulated with plasmid cloning deoxyribonucleic acid 3.1‐ZEB1‐AS1/microribonucleic acid (miR)‐181c‐5p mimic/short hairpin RNA specific to sirtuin 1 (sh‐SIRT1). ZEB1‐AS1, miR‐181c‐5p expression patterns, cell viability, collagen I and III, α‐smooth muscle actin (α‐SMA), fibronectin levels and cell migration were assessed by reverse transcription quantitative polymerase chain reaction, cell counting kit‐8, western blot and scratch tests. Nuclear/cytosol fractionation assay verified ZEB1‐AS1 subcellular localization. The binding sites between ZEB1‐AS1 and miR‐181c‐5p, and between miR‐181c‐5p and SIRT1 were predicted and verified by Starbase and dual‐luciferase assays. The binding of SIRT1 to Yes‐associated protein (YAP) and YAP acetylation levels were detected by co‐immunoprecipitation. Diabetic mouse models were established. SIRT1, collagen I, collagen III, α‐SMA and fibronectin levels, mouse myocardium morphology and collagen deposition were determined by western blot, and hematoxylin–eosin and Masson trichrome staining. Results Zinc finger E‐box binding homeobox 1 antisense 1 was repressed in HG‐induced HCFs. ZEB1‐AS1 overexpression inhibited HG‐induced HCF excessive proliferation, migration and fibrosis, and diminished collagen I, collagen III, α‐SMA and fibronectin protein levels in cells. miR‐181c‐5p had targeted binding sites with ZEB1‐AS1 and SIRT1. SIRT1 silencing/miR‐181c‐5p overexpression abrogated ZEB1‐AS1‐inhibited HG‐induced HCF proliferation, migration and fibrosis. ZEB1‐AS1 suppressed HG‐induced HCF fibrosis through SIRT1‐mediated YAP deacetylation. ZEB1‐AS1 and SIRT1 were repressed in diabetic mice, and miR‐181c‐5p was promoted. ZEB1‐AS1 overexpression improved myocardial fibrosis in diabetic mice, and reduced collagen I, collagen III, α‐SMA and fibronectin protein levels in myocardial tissues. Conclusion Long non‐coding ribonucleic acid ZEB1‐AS1 alleviated myocardial fibrosis through the miR‐181c‐5p–SIRT1–YAP axis in diabetic mice.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Long non‐coding ribonucleic acid zinc finger E‐box binding homeobox 1 antisense RNA 1 regulates myocardial fibrosis in diabetes through the Hippo–Yes‐associated protein signaling pathway

Lyu

Chen

et al. 2023

J of Diabetes Invest

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“…118 Overexpression of ZEB1-AS1 could regulate MAF bZIP transcription factor B (MAFB) expression by directly targeting miR-217, reducing HG-induced ECM accumulation in HK-2 cells, and inhibiting renal fibrosis in DKD. 119 However, MIAT was reported to be downregulated in expression in HK-2 cells in contrast to MCs and podocytes. Myocardial infarction-associated transcript expression levels were low and negatively correlated with serum creatinine (Scr) and blood urea nitrogen in both HK-2 cells and diabetic rats.…”

Section: Lncrnas With Downregulated Expression In Renal Tubular Epith...mentioning

confidence: 99%

“…ZEB1‐AS1 can promote H3K4me3 histone modification on the ZEB1 promoter to regulate ZEB1 118 . Overexpression of ZEB1‐AS1 could regulate MAF bZIP transcription factor B (MAFB) expression by directly targeting miR‐217, reducing HG‐induced ECM accumulation in HK‐2 cells, and inhibiting renal fibrosis in DKD 119 . However, MIAT was reported to be downregulated in expression in HK‐2 cells in contrast to MCs and podocytes.…”

Section: Lncrnas Affect Various Pathologic Changes In Dkdmentioning

confidence: 99%

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

Hou,

2024

Diabetes Metabolism Res

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Diabetic kidney disease (DKD), one of the common microvascular complications of diabetes, is increasing in prevalence worldwide and can lead to End‐stage renal disease. However, there are still gaps in our understanding of the pathophysiology of DKD, and both current clinical diagnostic methods and treatment strategies have drawbacks. According to recent research, long non‐coding RNAs (lncRNAs) are intimately linked to the developmental process of DKD and could be viable targets for clinical diagnostic decisions and therapeutic interventions. Here, we review recent insights gained into lncRNAs in pathological changes of DKD such as mesangial expansion, podocyte injury, renal tubular injury, and interstitial fibrosis. We also discuss the clinical applications of DKD‐associated lncRNAs as diagnostic biomarkers and therapeutic targets, as well as their limitations and challenges, to provide new methods for the prevention, diagnosis, and treatment of DKD.

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“…Synergizing with this mechanism, lncRNA ZEB1-AS1 that suppresses renal fibrosis, is downregulated in DN. Normally, ZEB1-AS1 sequesters miR-217 and upregulates the transcription factor MAFB (musculoaponeurotic fibrosarcoma oncogene homolog B) along with reduction in ECM proteins such as fibronectin and collagen, to inhibit renal fibrosis in DM [ 198 ]. The downregulation of ZEB1-AS1 favors renal fibrosis in DM.…”

Section: Lncrnas In Human Diseasesmentioning

confidence: 99%

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

Nadhan

Isidoro

Song

et al. 2022

Cells

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The cellular signaling network involves co-ordinated regulation of numerous signaling molecules that aid the maintenance of cellular as well as organismal homeostasis. Aberrant signaling plays a major role in the pathophysiology of many diseases. Recent studies have unraveled the superfamily of long non-coding RNAs (lncRNAs) as critical signaling nodes in diverse signaling networks. Defective signaling by lncRNAs is emerging as a causative factor underlying the pathophysiology of many diseases. LncRNAs have been shown to be involved in the multiplexed regulation of diverse pathways through both genetic and epigenetic mechanisms. They can serve as decoys, guides, scaffolds, and effector molecules to regulate cell signaling. In comparison with the other classes of RNAs, lncRNAs possess unique structural modifications that contribute to their diversity in modes of action within the nucleus and cytoplasm. In this review, we summarize the structure and function of lncRNAs as well as their vivid mechanisms of action. Further, we provide insights into the role of lncRNAs in the pathogenesis of four major disease paradigms, namely cardiovascular diseases, neurological disorders, cancers, and the metabolic disease, diabetes mellitus. This review serves as a succinct treatise that could open windows to investigate the role of lncRNAs as novel therapeutic targets.

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LncRNA ZEB1-AS1 inhibits renal fibrosis in diabetic nephropathy by regulating the miR-217/MAFB axis

Abstract: Diabetic nephropathy (DN) is a common chronic microvascular complication of diabetes, characterized by the deposition of extracellular matrix (ECM) proteins.

Cited by 7 publications

References 36 publications

Long non‐coding ribonucleic acid zinc finger E‐box binding homeobox 1 antisense RNA 1 regulates myocardial fibrosis in diabetes through the Hippo–Yes‐associated protein signaling pathway

Long non‐coding ribonucleic acid zinc finger E‐box binding homeobox 1 antisense RNA 1 regulates myocardial fibrosis in diabetes through the Hippo–Yes‐associated protein signaling pathway

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

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