PLoS One
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2025
·Vol. 20
·期 4
·e0319605
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IF 2.6
Hong-Fei He,Shuang Hou,Xiao-Ya Ma,Song-song Huang,Bo Yang,Jun-Kang Wang,Yuan Xu,Lei Tan,Hai-Yang Li
As one of the major causes of acute kidney injury, renal ischemia-reperfusion is a common health problem in a series of clinical situations, including renal transplantation. Although the mechanisms of renal IRI have been widely investigated, effective strategies are still in lacking for its prevention and treatment. In previous study, we found that the down-regulation of taurine upregulated gene 1, a long non-coding RNA (lncRNA TUG1), markedly alleviated renal IRI through mitigating the cell inflammation and apoptosis. At meanwhile, YTHDF2, an RNA methylation reading protein, was identified as a vital player in IRI of distinct organs, however, not reported in kidney. We then conducted the current study on the function of YTHDF2 in renal IRI and its regulatory role to TUG1. Based on renal IRI models in vitro and in vivo, dramatical down-regulation of YTHDF2 was presented. Subsequently, exogenous perturbation of YTHDF2 was conducted and its protective effects on cell apoptosis were demonstrated in acute IRI exogenous. Furthermore, with the same model, it was indicated that YTHDF2 protein negative regulated TUG1 RNA via direction interaction. Since then, YTHDF2 was proved as a potential protector of renal IRI through restraining of TUG1. In further speculation, induction of YTHDF2 in IRI will possibly become a possible strategy to combat the pathological process post renal transplantation or other clinical conditions.
研究领域:
分子生物学
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肾脏病学
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医学
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产品关联
DOI
PubMed
高影响因子
CARDIOVASCULAR PATHOLOGY
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2017
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IF 2.359
Lei Zhang,Hailing Cheng,Yuxia Yue,Shuangzhan Li,Daping Zhang,Ruili He
Background Long non-coding RNAs (lncRNAs) have been revealed to participate in the pathological events associated with atherosclerosis . However, the exact role of lncRNA taurine-up-regulated gene 1 (TUG1) and its possible molecular mechanism in atherosclerosis remain unidentified. Methods High-fat diet (HFD)-treated ApoE −/− mice were used as an in vivo model of atherosclerosis. Ox-LDL-induced macrophages and vascular smooth muscle cells (VSMCs) were employed as cell models of atherosclerosis. qRT-PCR was performed to detect the expression of TUG1 and miR-133a. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were analyzed by commercially available enzyme kits. Oil red O and hematoxylin and eosin (H&E) staining were conducted to examine atherosclerotic lesion. Luciferase reporter assay combined with RNA immunoprecipitation (RIP) was applied to confirm the interaction between TUG1, miR-133a and FGF1 . Cell proliferation ability was determined by Cell Counting Kit-8 (CCK-8) assay and trypan blue dye exclusion test. Cell apoptosis was evaluated with TUNEL assay. Expression and production of inflammatory cytokines was measured with western blot and ELISA analysis. Results TUG1 expression was up-regulated in HFD-treated ApoE −/− mice, as well as in ox-LDL-induced RAW264.7 and MOVAS cells. TUG1 knockdown inhibited hyperlipidemia , decreased inflammatory response, and attenuated atherosclerotic lesion in HFD-treated ApoE −/− mice. TUG1 could function as a molecular sponge of miR-133a to suppress its expression. TUG1 overexpression accelerated cell growth, improved inflammatory factor expression, and inhibited apoptosis in ox-LDL-stimulated RAW264.7 and MOVAS cells, while this effect was abated after transfection with miR-133 mimic. Moreover, fibroblast growth factor 1 (FGF1) was identified as a direct target of miR-133a. Restored expression of FGF1 overturned the effect of miR-133a on cell proliferation, inflammatory factor secretion and apoptosis in ox-LDL-treated RAW264.7 and MOVAS cells. Finally, TUG1 was revealed to up-regulate FGF1 expression by sponging miR-133a. Conclusion TUG1 knockdown ameliorates atherosclerosis by modulating FGF1 via miR-133a, raising the possibility of targeting TUG1 as an atheroprotective therapeutic strategy.
研究领域:
分子生物学
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心血管疾病
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遗传学
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产品关联
DOI
PubMed
高影响因子
HUMAN GENE THERAPY
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2020
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IF 4.51
Kaihua Zhai,Boyu Liu,Lin Gao
Long-noncoding RNA taurine upregulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of TUG1 in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+) in vitro and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. The expressions of TUG1, miR-152-3p, phosphatase and tensin homologue (PTEN), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction between TUG1 and miR-152-3p was analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model, TUG1 expression was upregulated and that of miR-152-3p was downregulated. Further research showed that TUG1 sponged and regulated miR-152-3p expression. Silencing of TUG1 not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation in vitro, pathological damage and neuroinflammation in vivo, but also suppressed the expressions of PTEN and cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP+-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by the miR-152-3p inhibitor. Thus, knocking down TUG1 might have a protective effect on PD through the miR-152-3p/PTEN pathway.
研究领域:
神经科学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2019
·Vol. 47
·期 1
·3511-3516
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IF 4.462
Shi H,Dong Z,Gao H
The aim of this study was to investigate whether lncRNA TUG1 could mediate the progression of ischemia-reperfusion injury following acute myocardial infraction. Mouse cardiomyocytes HL-1 cells were subjected to oxygen glucose deprivation followed by reperfusion (OGD/R) to induce myocardial I/R injury. The expression of TUG1 was detected by real-time PCR. Overexpression or down expression of TUG1 was performed in mouse HL-1 cardiomyocytes. The myocardial cell viability and apoptosis were respectively detected. In addition, the expression levels of inflammatory factors, apoptosis-related proteins and HMGB1 proteins were detected. Besides, an inhibitor of HMGB1 was used to treat cells to verify the relationship between TUG1 and HMGB1 protein. The expression of TUG1 was significantly up-regulated in OGD/R-induced myocardial HL-1 cells. The overexpression of TUG1-induced inflammation and apoptosis in OGD-R-induced myocardial HL-1 cells. Knock down of TUG1 protected OGD/R-induced myocardial I/R injury by inhibiting HMGB1 expression. Suppression of lncRNA TUG1 may prevent myocardial I/R injury following acute myocardial infarction via inhibiting HMGB1 expression.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
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