ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jing Li,Xiaojie Quan,Saifei Lei,Gang Chen,Jiawei Hong,Zhenyao Huang,Qi Wang,Weiyi Song,Xinxin Yang
Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10 −1 , 1, 10 μM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3 /miR-770/ PTX3 axis.
研究领域:
毒理学
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分子生物学
·
生殖健康
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2018
·
IF 3.977
Jian Fang,Qiuyan Chen,Baozhu He,Jiaxuan Cai,Yawen Yao,Yi Cai,Suowen Xu,Kannan R.R. Rengasamy,Shanmugaraj Gowrishankar,Shunmugiah Karutha Pandian,Tiansheng Cao
Tanshinone IIA is one of the most predominant bioactive constituents of Danshen , a traditional Chinese medicinal plant with multiple cardiovascular protective actions. Although Tanshinone IIA has been well documented for its endothelial protective efficacy, studies unveiling the mechanism and/or molecular targets for its pharmacological activity are still inadequate. In recent studies, it has been envisaged that the expression of pentraxin 3 (PTX3) was associated with atherosclerotic cardiovascular diseases (ACVD). Therefore, the current study was designed to evaluate the possible role of Tanshinone IIA in influencing the expression of PTX3 in endothelial cells and thereby prevents endothelial dysfunction . Molecular analyses through real-time PCR, western blot , and ELISA revealed that Tanshinone IIA down-regulates PTX3 gene expression as well as protein secretion in human endothelial cells in the presence or absence of TNF-α. Besides, Tanshinone IIA inhibits the adhesion of THP1 cells (a monocytic cell line) to activated-endothelial cells stimulated with TNF-α. Furthermore, mechanistic studies uncovered the role of p38 MAPK/NF-κB pathway in Tanshinone II-A mediated pharmacological effects. Thus, the present study exemplifies the manifestation of Tanshinone IIA as a plausible alternative natural remedy for ACVD by targeting PTX3.
研究领域:
药理学
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心血管疾病
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分子生物学
·
传统中药
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-20
·
IF 16.6
Han Xiao,Liu Lijuan,Huang Saihua,Xiao Wenfeng,Gao Yajing,Zhou Weitao,Zhang Caiyan,Zheng Hongmei,Yang Lan,Xie Xueru,Liang Qiuyan,Tu Zikun,Yu Hongmiao,Fu Jinrong,Wang Libo,Zhang Xiaobo,Qian Liling,Zhou Yufeng
N 6 -methyladenosine (m 6 A), the most prevalent mRNA modification, has an important function in diverse biological processes. However, the involvement of m 6 A in allergic asthma and macrophage homeostasis remains largely unknown. Here we show that m 6 A methyltransferases METTL3 is expressed at a low level in monocyte-derived macrophages from childhood allergic asthma patients. Conditional knockout of Mettl3 in myeloid cells enhances Th2 cell response and aggravates allergic airway inflammation by facilitating M2 macrophage activation. Loss and gain functional studies confirm that METTL3 suppresses M2 macrophage activation partly through PI3K/AKT and JAK/STAT6 signaling. Mechanistically, m 6 A-sequencing shows that loss of METTL3 impairs the m 6 A-YTHDF3-dependent degradation of PTX3 mRNA, while higher PTX3 expression positively correlates with asthma severity through promoting M2 macrophage activation. Furthermore, the METTL3/YTHDF3-m 6 A/PTX3 interactions contribute to autophagy maturation in macrophages by modulating STX17 expression. Collectively, this study highlights the function of m 6 A in regulating macrophage homeostasis and identifies potential targets in controlling allergic asthma.
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产品关联
DOI
PubMed
高影响因子
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