JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Rui Zhang,Jingyao Guo,Yupeng Wang,Rundong Sun,Guangzhu Dong,Xinru Wang,Guizhen Du
The increased usage of bisphenol S (BPS) results in wide distribution in pregnant women. In this study, pregnant mice were given multiple-dose BPS during gestation. Results showed that prenatal BPS exposure (50 μg/kg/day) induced increased weight gain, dyslipidemia, higher liver triglyceride (TG), adipocyte hypertrophy, and hepatic lipid deposition in male offspring . Exosomes play important roles in regulating lipid metabolism . Here, serum exosomes and adipose miRNA sequencing of male offspring indicated a remarkable decrease in miR-29a-3p expression. To clarify whether adipocyte-derived exosomes mediate hepatic lipid deposition, exosomes were extracted from BPS-treated adipocytes and co-cultured with hepatocytes. These exosomes could be taken up by hepatocytes and promoted lipid deposition, and notably, exosomal miR-29a-3p was downregulated. Furthermore, miR-29a-3p knockdown in adipocyte-derived exosomes promoted hepatocyte lipid deposition, whereas overexpression led to the opposite effect. Also, the role of miR-29a-3p was demonstrated in hepatocytes by overexpressing or knocking it down. Subsequent studies have shown that miR-29a-3p can promote lipid deposition by directly targeting Col4a1 . Taken together, prenatal BPS exposure could lead to lower miR-29a-3p yield in adipocyte-derived exosomes and decrease miR-29a-3p content transported to hepatocytes, which further negatively regulate Col4a1 and promote hepatic lipid deposition. Our findings provided clues to maternal environmental exposure-induced liver metabolic diseases.
研究领域:
毒理学
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分子生物学
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内分泌学
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发育生物学
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DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2022
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IF 4.271
Shuhong Guan,Hui Liu,Jun Zhou,Qiudi Zhang,Hui Bi
Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis . Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo , MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro , MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy.
研究领域:
肺科学
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分子生物学
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细胞生物学
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药理学
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DOI
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
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