Long noncoding RNA ENSRNOG00000037522 is involved in the podocyte epithelial‑mesenchymal transition in diabetic rats

Li, Ling; Tan, Zhen; Zhang, Changning; Gui, Shuyan; Hu, Yuanyuan; Chen, Libo

doi:10.3892/ijmm.2018.3457

Cited by 16 publications

(20 citation statements)

References 47 publications

(51 reference statements)

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“…For example, lncRNA ENSRNOG00000037522 is involved in the J Cell Physiol. 2019;234:12926-12933. wileyonlinelibrary.com/journal/jcp podocyte EMT process in diabetic rats (Ling et al, 2018). LncRNA CYP4B1-PS1-001 can regulate the proliferation and fibrosis in DN .…”

Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial‐to‐mesenchymal transition by targeting miR‐27b‐3p and ZEB1 in diabetic nephropathy

Wang

Zhu

et al. 2018

Journal Cellular Physiology

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Diabetic nephropathy (DN) is a kind of microvascular complications of diabetes. Long noncoding RNAs (lnRNAs) can participate in the development of various diseases, including DN. However, the function of lncRNA NEAT1 is unclear. In our present study, we reported that NEAT1 was significantly increased in streptozotocin‐induced DN rat models and high‐glucose‐induced mice mesangial cells. We observed that knockdown of NEAT1 greatly inhibited renal injury of DN rats. Meanwhile, downregulation of NEAT1‐modulated extracellular matrix (ECM) proteins (ASK1, fibronectin, and TGF‐β1) expression and epithelial–mesenchymal transition (EMT) proteins (E‐cadherin and N‐cadherin) in vitro. Previously, miR‐27b‐3p has been reported to be involved in diabetes. Here, miR‐27b‐3p was decreased in DN rats and high‐glucose‐induced mice mesangial cells. The direct correlation between NEAT1 and miR‐27b‐3p was validated using the dual‐luciferase reporter assay and RNA immunoprecipitation experiments. In addition, zinc finger E‐box binding homeobox 1 (ZEB1), which has been identified in the process of EMT clearly contributes to EMT progression. ZEB1 was predicted as a target of miR‐27b‐3p and overexpression of miR‐27b‐3p dramatically repressed ZEB1 expression. Therefore, our data implied the potential role of NEAT1 in the fibrogenesis and EMT in DN via targeting miR‐27b‐3p and ZEB1.

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Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial‐to‐mesenchymal transition by targeting miR‐27b‐3p and ZEB1 in diabetic nephropathy

Wang

Zhu

et al. 2018

Journal Cellular Physiology

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“…Long et al (8) reported that Tug1 regulates mitochondrial function in podocytes by the epigenetic targeting of the transcription factor peroxisome proliferator-activated receptor ␥ coactivator 1␣. Ling et al (9) showed that lncRNA ENSRNOG00000037522 is involved in the podocyte epithelial-mesenchymal transition in diabetic rats.…”

mentioning

confidence: 99%

The long noncoding RNA LOC105374325 causes podocyte injury in individuals with focal segmental glomerulosclerosis

Zhou

Han

Shi

et al. 2018

Journal of Biological Chemistry

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Focal segmental glomerulosclerosis (FSGS) is a common kidney disease that results in nephrotic syndrome. FSGS arises from dysfunction and apoptosis of podocytes in the glomerulus of the kidney, leading to podocytopathy. The molecular mechanisms underlying podocyte apoptosis remain incompletely understood. Using an array of gene expression profiling, PCR, and in situ hybridization assay, we found here that the levels of the long noncoding RNA LOC105374325 were elevated in the renal podocytes of individuals with FSGS. We also observed that the microRNAs miR-34c and miR-196a/b down-regulated the expression of the apoptosis regulators BCL2-associated X, apoptosis regulator (Bax), and BCL2 antagonist/killer 1 (Bak) in podocytes. Competitive binding between LOC105374325 and miR-34c or miR-196a/b increased Bax and Bak levels and caused podocyte apoptosis. Of note, the mitogen-activated protein kinase P38 and the transcription factor CCAAT enhancer-binding protein ␤ (C/EBP␤) up-regulated LOC105374325 expression. P38 inhibition or C/EBP␤ silencing decreased LOC105374325 levels and inhibited apoptosis in adriamycin-treated podocytes. LOC105374325 overexpression decreased miR-34c and miR-196a/b levels, increased Bax and Bak levels, and induced proteinuria and focal segmental lesions in mice. In conclusion, activation of the P38/C/ EBP␤ pathway stimulates the expression of LOC105374325, which, in turn, increases Bax and Bak levels and causes apoptosis by competitively binding to miR-34c and miR-196a/b in the podocytes of individuals with FSGS.

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“…Many studies have reported relationships between lncRNAs and DN. For instance, overexpression of the lncRNAs ENSMUST00000147869 and cytochrome P450, family 4, subfamily b, polypeptide 1, pseudogene 1 (CYP4B1-PS1-001) was reported to inhibit the proliferation and fibrosis of mouse MCs in DN (26,27); the lncRNAs myocardial infarction associated transcript (MIAT) and plasmacytoma variant translocation 1 (Pvt1) were reported to regulate renal tubular epithelial injury and ECM accumulation in DN (28,29); silencing of the lncRNAs ENSRNOG00000037522 and long intergenic non-protein coding RNA 1619 (LINC01619) was reported to partially restore podocyte damage in DN (30,31); silencing of the lncRNA erb-b2 receptor tyrosine kinase 4-IR9 (Erbb4-IR9) prevented kidney damage and fibrosis in DN via miR-29b (32); the lncRNA Gm4419 affected DN mesangial proliferation by binding to the subunit P50 of NF-kB (33); and the lncRNA Pvt1 was reported to contribute to susceptibility to DN through a genome-wide analysis of single-nucleotide polymorphisms (34). Thus, these results suggest that lncRNAs play important roles in the pathogenesis of DN.…”

Section: Discussionmentioning

confidence: 99%

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

et al. 2019

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Evidence has shown that long noncoding RNAs (IncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of IncRNAs on mesangial cell (MC) proliferation in DN‐related ceRNA networks. Differences in IncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA‐seq, and DN‐related IncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real‐time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5‐ethynyl‐2′‐deoxyuridine (EdU) in MCs cultured under high‐ or low‐glucose conditions. Moreover, the effect of the topological key IncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)‐449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 IncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN‐related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of IncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA‐seq and real‐time qPCR in vivo and in vitro. miR‐449a and miR‐449b, which were down‐regulated in MCs cultured with high glucose, were selected for further analysis. The results of real‐time qPCR and luciferase assay revealed the IncRNA H2k2‐miR‐449a/b‐Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR‐449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key IncRNA H2k2 in the DN‐related ceRNA network and the miR‐449a/b/Trim11/Mek signaling pathway during MC proliferation in DN.—Chen, W., Peng, R., Sun, Y., Liu, H., Zhang, L., Peng, H., Zhang, Z. The topological key IncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR‐449a/b/Trim11/Mek signaling pathway. FASEB J. 33, 11492–11506 (2019). http://www.fasebj.org

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Long noncoding RNA ENSRNOG00000037522 is involved in the podocyte epithelial‑mesenchymal transition in diabetic rats

Cited by 16 publications

References 47 publications

LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial‐to‐mesenchymal transition by targeting miR‐27b‐3p and ZEB1 in diabetic nephropathy

LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial‐to‐mesenchymal transition by targeting miR‐27b‐3p and ZEB1 in diabetic nephropathy

The long noncoding RNA LOC105374325 causes podocyte injury in individuals with focal segmental glomerulosclerosis

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

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