TISSUE & CELL
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2022
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IF 2.586
Jie Pan,Xiaoping Cai,Xiao Zheng,Xiaoyu Zhu,Jihong Feng,Xiaoqiu Wang
Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.
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PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Xiang Li,Longlong Wu,Xuan Tian,Weiping Zheng,Mengshu Yuan,Xiaorong Tian,Huaiwen Zuo,Hongli Song,Zhongyang Shen
Hepatic ischemia-reperfusion injury (IRI) is an inevitable result of liver surgery. Steatotic livers are extremely sensitive to IRI and have worse tolerance. Ferroptosis is considered to be one of the main factors of organ IRI. This study is aimed at exploring the role of ferroptosis in the effect of heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) on steatotic liver IRI and its mechanism. An IRI model of a steatotic liver and a hypoxia reoxygenation (HR) model of steatotic hepatocytes (SHPs) were established. Rat BMMSCs were extracted and transfected with the Ho1 gene to establish HO-1/BMMSCs, and their exosomes were extracted by ultracentrifugation. Ireb2 was knocked down to verify its role in ferroptosis and cell injury in SHP-HR. Public database screening combined with quantitative real-time reverse transcription PCR identified microRNAs (miRNAs) targeting Ireb2 in HO-1/BMMSCs exosomes. miR-29a-3p mimic and inhibitor were used for functional verification experiments. Liver function, histopathology, terminal deoxynulceotidyl transferase nick-end-labeling staining, cell viability, mitochondrial membrane potential, and cell death were measured to evaluate liver tissue and hepatocyte injury. Ferroptosis was assessed by detecting the levels of IREB2, Fe2+, malondialdehyde, glutathione, lipid reactive oxygen species, glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2 mRNA, and mitochondrial morphology. The results revealed that HO-1/BMMSCs improved liver tissue and hepatocyte injury and suppressed ferroptosis in vivo and in vitro. The expression of IREB2 was increased in steatotic liver IRI and SHP-HR. Knocking down Ireb2 reduced the level of Fe2+ and inhibited ferroptosis. HO-1/BMMSC exosomes reduced the expression of IREB2 and inhibited ferroptosis and cell damage. Furthermore, we confirmed high levels of miR-29a-3p in HO-1/BMMSCs exosomes. Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis. Downregulation of miR-29a-3p blocked the protective effect of HO-1/BMMSC exosomes on SHP-HR cell injury. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic liver IRI. HO-1/BMMSCs could suppress ferroptosis by targeting Ireb2 via the exosomal transfer of miR-29a-3p.
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高影响因子
Redox Biology
·
2025
·
IF 11.9
Dan Liu,Hui Yu,Zhicun Liu,Le Wang,Dawo Liu,Xiangyu Cao
Acrolein is a significant high priority hazardous air pollutant. This research explore the relationship of acrolein-induced ferroptosis with the pathogenesis of lung injury by combining cellular, transcriptome, and animal-level studies. The results in vivo and in vitro models indicated that a total of 18,868 differenced lncRNAs and 15,639 differenced mRNAs were obtained after acrolein exposure. After screening, 636 lncRNAs and 214 mRNAs were obviously different of the acrolein injured group with the control group. Differential genes were mainly enriched in the iron ion binding, tissue homeostasis, etc. Among them, lncRNA MIR155HG significantly responded to the toxic effects of acrolein, the knockdown of lncRNA MIR155HG could inhibit miR-155-5p expression, promote CD200R1 expression, and improve cell viability. Furthermore, it effectively inhibited acrolein-induced the activation of ferroptosis pathway in BEAS-2B cells and lung tissue, indicating that lncRNA MIR155HG might be a potential new target for the inhibition of acrolein toxicity. LncRNA-MIR155HG/miR-155-5p/CD200R1 axis played an significant role in the lung injury, and induced ferroptosis by regulating the Nrf2/SLC7A11/GPX4 pathway. This study is the first to reveal that acrolein exposure significantly affected lncRNA and mRNA expression in BEAS-2B cells, and found that lncRNA MIR155HG effectively regulated acrolein-induced ferroptosis pathway, providing novel insights for the treatment of lung injury.
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高影响因子
PHYTOMEDICINE
·
2026
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IF 11.3
Tingwen Zhang,Ruihong Zou,Zheng Chen,Yawei Li,Xin Sun,Xialin Sun
Background Overuse of acetaminophen (APAP) can induce acute liver injury (ALI), and its mechanism is closely related to ferroptosis. 4′-O-β-D-glucosyl-5-O-methylvisamminol (5-O) is a natural coumarin glycoside with anti-inflammatory and antioxidant activities, but whether it can alleviate liver injury through intervention in ferroptosis and multi-dimensional mechanisms remains unclear. Purpose To explore whether 5-O can alleviate APAP-induced ALI through multiple mechanisms such as inhibiting ferroptosis, regulating inflammation, promoting lipid metabolism, and reshaping the intestinal microbiota . Methods Through in vitro and in vivo experiments, combined with CCK-8, Western blot, whole transcriptome sequencing, 16S rRNA sequencing, FMT and other techniques and methods, the mechanism of 5-O was evaluated from multiple levels such as cells, tissues, metabolism and flora. Results 5-O downregulated Tfrc/Slc39a14 in cells to reduce iron intake and upregulated Slc7a11/GPX4 to enhance antioxidant capacity. It reduced serum ALT/AST, alleviated liver tissue pathological damage, inhibited the expression of chemokines and inflammatory factors, and activated the PPARα-Fabp1/Me1 axis to promote lipid metabolism. Whole transcriptome analysis revealed that 5-O intervention was associated with upregulation of miR-30e-3p and downregulation of Tfrc, suggesting a potential role in modulating iron metabolism. Concurrently, the analysis indicated that 5-O treatment was linked to inhibition of the ferroptosis pathway and activation of the PPAR pathway. In addition, 5-O reshaped the intestinal microbiota, inhibited pro-inflammatory bacterial genera, and promoted the colonization of the probiotic Lactobacillus . Conclusion This study systematically clarified that the hepatoprotective effect of 5-O against APAP-induced liver injury is associated with a multi-dimensional network involving "ferroptosis-inflammation-metabolism-flora". The innovation lies in systematically elucidating the multi-faceted actions of a natural product, which may involve regulating ferroptosis through miR-30e-3p associated changes, cross-organ metabolic reprogramming, and microecological modulation. This work provides a candidate drug with multi-dimensional synergistic potential for the prevention and treatment of liver injury.
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高影响因子
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