Increased HERV-E clone 4–1 expression contributes to DNA hypomethylation and IL-17 release from CD4+ T cells via miR-302d/MBD2 in systemic lupus erythematosus
Identifieur interne : 000736 ( Main/Exploration ); précédent : 000735; suivant : 000737Increased HERV-E clone 4–1 expression contributes to DNA hypomethylation and IL-17 release from CD4+ T cells via miR-302d/MBD2 in systemic lupus erythematosus
Auteurs : Xin Wang [République populaire de Chine] ; Chaoshuai Zhao [République populaire de Chine] ; Chengzhong Zhang [République populaire de Chine] ; Xingyu Mei [République populaire de Chine] ; Jun Song [République populaire de Chine] ; Yue Sun [République populaire de Chine] ; Zhouwei Wu [République populaire de Chine] ; Weimin Shi [République populaire de Chine]Source :
- Cell Communication and Signaling : CCS [ 1478-811X ] ; 2019.
Abstract
Increased human endogenous retroviruses E clone 4–1 (HERV-E clone 4–1) mRNA expression is observed in systemic lupus erythematosus (SLE) patients and associates with the disease activity. In this study, we want to further investigate the mechanism of HERV-E clone 4–1 mRNA upregulation and its roles in SLE progression.
CD4+ T cells were isolated from venous blood of SLE patients or healthy controls and qRT-PCR was used to detect HERV-E clone 4–1 mRNA expression. We then investigated the regulation of Nuclear factor of activated T cells 1 (NFAT1) and Estrogen receptor-α (ER-α) on HERV-E clone 4–1 transcription and the functions of HERV-E clone 4–1 3′ long terminal repeat (LTR) on DNA hypomethylation and IL-17 release.
We found HERV-E clone 4–1 mRNA expression was upregulated in CD4+ T cells from SLE patients and positively correlated with SLE disease activity. This is associated with the activation of Ca2+/calcineurin (CaN)/NFAT1 and E2/ER-α signaling pathway and DNA hypomethylation of HERV-E clone 4–1 5’LTR. HERV-E clone 4–1 also takes part in disease pathogenesis of SLE through miR-302d/Methyl-CpG binding domain protein 2 (MBD2)/DNA hypomethylation and IL-17 signaling via its 3’LTR.
HERV-E clone 4–1 mRNA upregulation is due to the abnormal inflammation/immune/methylation status of SLE and it could act as a potential biomarker for diagnosis of SLE. HERV-E clone 4–1 also takes part in disease pathogenesis of SLE via its 3’LTR and the signaling pathways it involved in may be potential therapeutic targets of SLE.
The online version of this article (10.1186/s12964-019-0416-5) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12964-019-0416-5
PubMed: 31412880
PubMed Central: 6694475
Affiliations:
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wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Chengzhong" sort="Zhang, Chengzhong" uniqKey="Zhang C" first="Chengzhong" last="Zhang">Chengzhong Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Mei, Xingyu" sort="Mei, Xingyu" uniqKey="Mei X" first="Xingyu" last="Mei">Xingyu Mei</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Song, Jun" sort="Song, Jun" uniqKey="Song J" first="Jun" last="Song">Jun Song</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Yue" sort="Sun, Yue" uniqKey="Sun Y" first="Yue" last="Sun">Yue Sun</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Zhouwei" sort="Wu, Zhouwei" uniqKey="Wu Z" first="Zhouwei" last="Wu">Zhouwei Wu</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Shi, Weimin" sort="Shi, Weimin" uniqKey="Shi W" first="Weimin" last="Shi">Weimin Shi</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai 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Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Chaoshuai" sort="Zhao, Chaoshuai" uniqKey="Zhao C" first="Chaoshuai" last="Zhao">Chaoshuai Zhao</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Chengzhong" sort="Zhang, Chengzhong" uniqKey="Zhang C" first="Chengzhong" last="Zhang">Chengzhong Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Mei, Xingyu" sort="Mei, Xingyu" uniqKey="Mei X" first="Xingyu" last="Mei">Xingyu Mei</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Song, Jun" sort="Song, Jun" uniqKey="Song J" first="Jun" last="Song">Jun Song</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Yue" sort="Sun, Yue" uniqKey="Sun Y" first="Yue" last="Sun">Yue Sun</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Zhouwei" sort="Wu, Zhouwei" uniqKey="Wu Z" first="Zhouwei" last="Wu">Zhouwei Wu</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Shi, Weimin" sort="Shi, Weimin" uniqKey="Shi W" first="Weimin" last="Shi">Weimin Shi</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai, 200080 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell Communication and Signaling : CCS</title><idno type="eISSN">1478-811X</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">Increased human endogenous retroviruses E clone 4–1 (HERV-E clone 4–1) mRNA expression is observed in systemic lupus erythematosus (SLE) patients and associates with the disease activity. In this study, we want to further investigate the mechanism of HERV-E clone 4–1 mRNA upregulation and its roles in SLE progression.</p></sec><sec><title>Methods</title><p id="Par2">CD4<sup>+</sup> T cells were isolated from venous blood of SLE patients or healthy controls and qRT-PCR was used to detect HERV-E clone 4–1 mRNA expression. We then investigated the regulation of Nuclear factor of activated T cells 1 (NFAT1) and Estrogen receptor-α (ER-α) on HERV-E clone 4–1 transcription and the functions of HERV-E clone 4–1 3′ long terminal repeat (LTR) on DNA hypomethylation and IL-17 release.</p></sec><sec><title>Results</title><p id="Par3">We found HERV-E clone 4–1 mRNA expression was upregulated in CD4<sup>+</sup> T cells from SLE patients and positively correlated with SLE disease activity. This is associated with the activation of Ca<sup>2+</sup>/calcineurin (CaN)/NFAT1 and E2/ER-α signaling pathway and DNA hypomethylation of HERV-E clone 4–1 5’LTR. HERV-E clone 4–1 also takes part in disease pathogenesis of SLE through miR-302d/Methyl-CpG binding domain protein 2 (MBD2)/DNA hypomethylation and IL-17 signaling via its 3’LTR.</p></sec><sec><title>Conclusions</title><p id="Par4">HERV-E clone 4–1 mRNA upregulation is due to the abnormal inflammation/immune/methylation status of SLE and it could act as a potential biomarker for diagnosis of SLE. HERV-E clone 4–1 also takes part in disease pathogenesis of SLE via its 3’LTR and the signaling pathways it involved in may be potential therapeutic targets of SLE.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1186/s12964-019-0416-5) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yin, Y" uniqKey="Yin Y">Y Yin</name></author><author><name sortKey="Choi, S" uniqKey="Choi S">S Choi</name></author><author><name sortKey="Xu, Z" uniqKey="Xu Z">Z Xu</name></author><author><name sortKey="Perry, D" uniqKey="Perry D">D Perry</name></author><author><name sortKey="Seay, H" uniqKey="Seay H">H Seay</name></author><author><name sortKey="Croker, B" uniqKey="Croker B">B Croker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaul, A" uniqKey="Kaul A">A 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Jun" uniqKey="Song J" first="Jun" last="Song">Jun Song</name><name sortKey="Sun, Yue" sort="Sun, Yue" uniqKey="Sun Y" first="Yue" last="Sun">Yue Sun</name><name sortKey="Wu, Zhouwei" sort="Wu, Zhouwei" uniqKey="Wu Z" first="Zhouwei" last="Wu">Zhouwei Wu</name><name sortKey="Zhang, Chengzhong" sort="Zhang, Chengzhong" uniqKey="Zhang C" first="Chengzhong" last="Zhang">Chengzhong Zhang</name><name sortKey="Zhao, Chaoshuai" sort="Zhao, Chaoshuai" uniqKey="Zhao C" first="Chaoshuai" last="Zhao">Chaoshuai Zhao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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