FISH & SHELLFISH IMMUNOLOGY
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2022
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IF 4.622
Zhiying Miao,Zhiruo Miao,Xiaohua Teng,Shiwen Xu
Lead (Pb) has been concerned as one of the most severe hazardous contaminants, because it can cause pyroptosis in multiple tissues of mammals and birds. Melatonin (Mel) has attracted much interest for its role in governing intestinal injury via microRNAs (miRNAs). To explore the effect of Mel on Pb exposure-induced intestinal epithelial cell pyroptosis in common carps by regulating miR-17-5p/TXNIP axis, the Pb exposure and Pb-Mel treated models were constructed in vivo . The results elucidated that the suppressed expression of miR-17-5p and intensified level of TXNIP were primarily detected in Pb-exposed gut tissues, and both abolished with Mel addition, along with downregulated Pb-mediated elevated expression of NLRP3, CASP1, IL1β and GSDMD. Additionally, the targeting relationship between miR-17-5p and TXNIP were demonstrated by dual-luciferase reporter assay, and on this basis, miR-17-5p NC, mimic and inhibitor cell models were established. Thereby, Thereby, the expression of TXNIP in the miR-17-5p mimic groups was significant lower in the Pb-exposure but still elevated than the Control group, and the expression of NLRP3 and NLRP3-dependent pyrotposis-related genes performed consistent alterations. Noticeably, the expression of TXNIP suppressed with Mel addition even in the miR-17-5p inhibitor cell model, resulting in the inactivation of NLRP3 inflammasome-dependent pyroptosis. Overall, we draw the conclusion as Mel attenuates Pb-induced intestinal epithelial cell pyroptosis via miR-17-5p/TXNIP axis. The present study provides a novel perspective for toxicological mechanism of Pb, and new insights for the detoxification mechanism of Mel.
研究领域:
毒理学
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分子生物学
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水生生物学
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环境科学
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DOI
PubMed
高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·1-18
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IF 15.7
Li Wen,Shi Zhiyuan,Jing Huaqing,Dou Yunsheng,Liu Xinyi,Zhang Mengyao,Qiu Zitong,Heger Zbynek,Li Nan
Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.
研究领域:
医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Clinical Interventions in Aging
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2021
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IF 4.458
Junyang Chen,Xuefeng Li,Feng Zhao,Yubo Hu
Background Propofol (PPF) ameliorates ischemia/reperfusion (I/R) injury in multiple organs by reducing apoptosis and release of pro-inflammatory cytokines. This study aims to explore the mechanism of PPF in attenuating myocardial ischemia-reperfusion injury (MIRI). Materials and Methods Rat MIRI model was established, and PPF pre-treatment was performed 10 min before I/R. H9c2 cardiomyocytes treated with hypoxia/reoxygenation (H/R) were used to establish an in vitro model. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate HOTAIR and miR-17-5p expression levels. Flow cytometry was employed to detect the apoptosis of H9c2 cells. The interaction between HOTAIR and miR-17-5p was determined by bioinformatics analysis, luciferase reporter gene analysis, and RNA immunoprecipitation experiments. STAT3 and p-STAT3 expressions were detected by Western blot. Results PPF pre-treatment significantly reduced creatine kinase isoenzyme (CK-MB) and serum lactate dehydrogenase (LDH) levels in the serum of the rats with MIRI. PPF pre-treatment remarkably up-regulated HOTAIR expression and down-regulated miR-17-5p expression in both in vivo and in vitro models. HOTAIR adsorbed miR-17-5p to repress the expression of miR-17-5p. PPF pre-treatment markedly inhibited cardiomyocyte apoptosis induced by I/R or H/R. HOTAIR knockdown could partially reverse the protective effects of PPF on MIRI. HOTAIR could activate STAT3 signaling via repressing miR-17-5p expression. Conclusion PPF protects the MIRI by modulating the HOTAIR/miR-17-5p/STAT3 axis.
研究领域:
药理学
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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
JOURNAL OF MOLECULAR HISTOLOGY
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2021
·Vol. 52
·期 5
·1007-1020
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IF 2.611
Wang Zizhang,Chen Xu,Liang Qinlong,An Yuan,Wei Meng,Shi Wei
Glioma remains the most common malignant tumors in the central nervous system and often has poor prognosis. In recent years, it has been gradually revealed that non-coding RNA effects glioma progression. In this study, we aimed to investigate the significance of circular RNA TLK1 (Circ-TLK1) in predicting the survival of glioma patients as well as its role in glioma development via both in-vitro and in-vivo experiments. We found that Circ-TLK1 was conspicuously up-regulated in glioma tissues compared with adjacent normal tissues, and the up-regulated Circ-TLK1 was significantly correlated with glioma patients’ larger tumor volume and higher grades. Functionally, Circ-TLK1 over-expression facilitated glioma growth, migration and invasion, inhibited cell apoptosis, and accelerated PANX1/MAPK/ERK expression, while Circ-TLK1 low expression had the opposite effects. In addition, bioinformatics analysis showed that miR-17-5p was a potential target of Circ-TLK1 and targeted at PANX1. Furthermore, through dual luciferase viability assay, Circ-TLK1 acted as a competing endogenous RNA by sponging miR-17-5p, which targeted and inhibited PANX1/MAPK/ERK expression. MiR-17-5p overexpression mitigated glioma progression, which was significantly inhibited with Circ-TLK1 upregulation. In conclusion, this study confirmed a novel axis of Circ-TLK1-miR-17-5p-PANX1 in modulating glioma development, providing more references for glioma diagnosis and targeted therapy.
研究领域:
肿瘤学
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分子生物学
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神经科学
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DOI
PubMed
高影响因子
Virulence
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2026
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IF 6.8
Xinxian Wang,Shurui Yang,Lichun Xie,Shanshan Qi,Libo Gao,Yongmei Li,Qian Li,Junlong Bi,Jianping Liu,Yongneng Li,Gefen Yin
Classical swine fever virus (CSFV) remains a major threat to the global swine industry, yet the involvement of host miRNAs in its pathogenic mechanisms is not fully understood. In this study, we demonstrate for the first time that miR-17-5p inhibits CSFV replication through an autophagy-dependent mechanism by targeting polycystin-2 (PKD2), a key calcium channel protein that regulates the AMPK/mTOR signaling pathway. Using the PK-15 cell model, we found that CSFV infection significantly upregulates miR-17-5p expression. Functional assays revealed that miR-17-5p exerts antiviral effects by directly binding to the 3’-UTR of PKD2, as confirmed by bioinformatics prediction and dual-luciferase reporter assays. Silencing of PKD2 recapitulated the antiviral effect of miR-17-5p overexpression, while PKD2 reconstitution restored viral replication by activating AMPK signaling and suppressing mTOR activity, thereby significantly enhancing autophagic flux – as evidenced by increased LC3-II/I ratio and decreased p62 levels. Mechanistically, PKD2 regulates intracellular calcium dynamics, modulating the AMPK/mTOR-autophagy axis to promote CSFV proliferation. This work uncovers a novel host antiviral mechanism in which a miRNA controls virus-induced autophagy via calcium signaling. To our knowledge, this is the first report to establish the pivotal role of miRNA-mediated calcium signaling modulation in flavivirus-host interactions. These findings provide a mechanistic framework and potential therapeutic targets for anti-CSFV interventions focused on PKD2 or autophagy regulation.
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产品关联
DOI
PubMed
高影响因子
Aging-US
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2021
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IF 5.682
Feng Zhang,Feili Lin,Zhiwen Xu,Zheng Huang
Intervertebral disc degeneration (IDD) is the prevailing spine disorder and is associated with musculoskeletal disease. The extracellular matrix (ECM) degradation is an essential hallmark of IDD progression. Circular RNAs (circRNAs), as crucial cellular regulators, participate in multiple pathological processes including IDD. Here, we tried to explore the effect of circITCH on the ECM degradation of IDD and the underlying mechanism. Significantly, the expression levels of circITCH were elevated in the IDD patients’ nucleus pulposus (NP) tissues relative to that of normal cases. CircITCH promoted apoptosis and decreased proliferation of NP cells. CircITCH contributed to ECM degradation, as demonstrated by increased ADAMTS4 and MMP13 expression and decreased aggrecan and collagen II expression. Mechanically, miR-17-5p could be sponged by circITCH and miR-17-5p inhibited ECM degradation by repressing SOX4 in degenerative NP cells. CircITCH could activate Wnt/β-catenin pathway by targeting miR-17-5p/SOX4 signaling. SOX4 overexpression, miR-17-5p inhibitor, or Wnt/β-catenin signaling activator LiCl was able to reverse circITCH knockdown-inhibited apoptosis and ECM degradation, and circITCH knockdown-enhanced proliferation in NP cells. Thus, we conclude that circITCH promotes ECM degradation in IDD by activating Wnt/β-catenin through miR-17-5p/SOX4 signaling. Our finding presents novel insight into the mechanism that circITCH modulates the IDD progression. CircITCH and SOX4 may serve as potential targets for IDD therapy.
研究领域:
医学遗传学
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骨科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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