Journal of Inflammation Research
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2023
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IF 4.5
Dongsheng Zhu,Zhitao Zhu,Han Qi
Objective Long non-coding RNA plays an important role in osteogenic differentiation. Nuclear enriched abundant transcript 1 (NEAT1) has been revealed to promote osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism remains unknown in acute suppurative osteomyelitis of children.Methods Osteogenic medium (OM) was used to induce osteogenic differentiation. Quantitative real-time PCR and Western blotting were used to evaluate gene expression. The effects of NEAT1, microRNA 339–5p (miR-339-5p), and salmonella pathogenicity island 1 (SPI1) on osteogenic differentiation were assessed in vitro using alizarin red S staining assays and alkaline phosphatase activity. Interactions between NEAT1, miR-339-5p, and SPI1 were identified using immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation.Results During osteogenic differentiation, expression of NEAT1 was up-regulated in hBMSCs, and miR-339-5p level was down during osteogenic differentiation. Knockdown of NEAT1 reduced the osteogenic differentiation of hBMSCs, and down-regulation of miR-339-5p may counteract the effect of NEAT1 silencing. SPI1 was a target of miR-339-5p by luciferase reporter assay and was also a transcription factor of NEAT1 by chromatin immunoprecipitation. A positive NEAT1-miR-339-5p-SPI1 feedback loop was found to be present during osteogenic differentiation in hBMSCs.Conclusion It was the first study to reveal that the NEAT1-miR-339-5p-SPI1 feedback loop can promote osteogenic differentiation in hBMSCs and shed a new light on the role of NEAT1 during osteogenic differentiation.
研究领域:
分子生物学
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细胞生物学
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医学遗传学
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儿科
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 2
·1667
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IF 5.6
Shengqi Huo,Qian Wang,Wei Shi,Lulu Peng,Yue Jiang,Mengying Zhu,Junyi Guo,Dewei Peng,Moran Wang,Lintong Men,Bingyu Huang,Jiagao Lv,Li Lin
Cuproptosis resulting from copper (Cu) overload has not yet been investigated in diabetic cardiomyopathy (DCM). Advanced glycosylation end products (AGEs) induced by persistent hyperglycemia play an essential role in cardiotoxicity. To clarify whether cuproptosis was involved in AGEs-induced cardiotoxicity, we analyzed the toxicity of AGEs and copper in AC16 cardiomyocytes and in STZ-induced or db/db-diabetic mouse models. The results showed that copper ionophore elesclomol induced cuproptosis in cardiomyocytes. It was only rescued by copper chelator tetrathiomolybdate rather than by other cell death inhibitors. Intriguingly, AGEs triggered cardiomyocyte death and aggravated it when incubated with CuCl2or elesclomol–CuCl2. Moreover, AGEs increased intracellular copper accumulation and exhibited features of cuproptosis, including loss of Fe–S cluster proteins (FDX1, LIAS, NDUFS8 and ACO2) and decreased lipoylation of DLAT and DLST. These effects were accompanied by decreased mitochondrial oxidative respiration, including downregulated mitochondrial respiratory chain complex, decreased ATP production and suppressed mitochondrial complex I and III activity. Additionally, AGEs promoted the upregulation of copper importer SLC31A1. We predicted that ATF3 and/or SPI1 might be transcriptional factors of SLC31A1 by online databases and validated that by ATF3/SPI1 overexpression. In diabetic mice, copper and AGEs increases in the blood and heart were observed and accompanied by cardiac dysfunction. The protein and mRNA profile changes in diabetic hearts were consistent with cuproptosis. Our findings showed, for the first time, that excessive AGEs and copper in diabetes upregulated ATF3/SPI1/SLC31A1 signaling, thereby disturbing copper homeostasis and promoting cuproptosis. Collectively, the novel mechanism might be an alternative potential therapeutic target for DCM.Keywords:cuproptosis;advanced glycosylation end products;diabetic cardiomyopathy;SLC31A1
研究领域:
心脏病学
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糖尿病
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分子生物学
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细胞信号传导
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病理生理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Xinyi Li,Hui Song,Yiwen Yuan,Na Jiang,Wei Duan,Tianzhao Xu,Chang Liu,Xinghui Liu
Cardiovascular diseases have long posed a significant threat to public health. Among them, myocarditis is a major category of cardiovascular disorders that is characterized by high mortality during its acute phase, necessitating urgent medical attention. This study aims to explore the therapeutic effects and underlying mechanisms of Spi1-mediated gene regulation in chemotherapy induced cardiomyopathy. To validate our findings, we employed bioinformatics analysis methods and established myocarditis models using the chemotherapeutic drug doxorubicin in both cellular and animal models. Our results demonstrated that the inhibition of Spi1 significantly suppressed inflammatory factor expression in H9C2 rat cardiomyocytes. Furthermore, in C57BL/6 mouse model, Spi1 inhibition was shown to improve cardiac function and alleviate both myocardial inflammation and fibrosis in mice with doxorubicin-induced myocarditis. Mechanistic investigations revealed that Spi1 suppression altered the expression of genes associated with immune response, cell differentiation and proliferation. Notably, Spi1 modulates the expression of YTHDF2, thereby influencing the PI3K/AKT/mTOR signaling pathway and subsequently regulating the inflammatory response. Collectively, these findings suggest that Spi1 plays a pivotal role in doxorubicin-induced myocarditis by mitigating inflammatory responses and myocardial injury through the regulation of YTHDF2 and the PI3K/AKT/mTOR signaling pathways, offering a promising therapeutic target for the treatment of myocarditis.
研究领域:
心血管研究
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分子生物学
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药理学
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肿瘤学
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信号转导
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产品关联
DOI
PubMed
高影响因子
iScience
·
2026
·Vol. 29
·期 7
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IF 4.5
Wujin Li,Changjian Lin,Hang Xu,Wenxiang Yue,Yi Xu,Baosong Xie,Daxuan Wang
Sulforaphane (SF) suppresses NSCLC metastasis by modulating miR-616-5p, which is transcriptionally upregulated by the oncogenic transcription factor SPI1. However, the roles of SF, SPI1, and miR-616-5p in NSCLC metastasis remain unclear. In this study, we found that SPI1 expression in NSCLC tissues positively correlated with miR-616-5p levels, and that SPI1 transcriptionally regulated miR-616-5p to promote NSCLC cell invasion and migration. Further analysis showed that SF directly binds SPI1, inhibiting its activity and downregulating miR-616-5p expression, thereby attenuating NSCLC metastasis. However, the poor stability of SF limits its clinical application. To address this, we developed a mesoporous silica nanoparticle (MSN)-based delivery system modified with hyaluronic acid and folic acid (MSNs@SF-HA-FA), which exhibited good stability, enhanced cellular uptake, and improved tumor targeting and anti-metastatic efficacy in NSCLC xenograft models. Collectively, our findings reveal the SPI1/miR-616-5p axis drives NSCLC metastasis and show that MSNs@SF-HA-FA enhances SF′s anti-metastatic effect, highlighting its clinical potential.
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DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Yao Li,Zi-Yu Liang,Hai-Lin Wang
Summary Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2′-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1. Mechanistic studies suggested that 6mdA enhances and prolongs the activation of erythropoiesis-associated master gene c-Kit and its downstream signaling, leading to expansion and accumulation of EPCs. Collectively, we demonstrate that 6mdA can efficiently stimulate the EPC hyperproliferation and provide a new regenerative medicine recipe to improve ex vivo generation of red blood cells.
研究领域:
血液学
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分子生物学
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再生医学
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细胞生物学
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DOI
PubMed
高影响因子
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