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著作: Shetty Abhishek/Venkatesh Thejaswini/[堤 理恵]/Suresh Padmanaban S/Gene expression changes and promoter methylation with the combined effects of estradiol and leptin in uterine tissue of the ovariectomized mice model of menopause./[Molecular Biology Reports]

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EOID
991419
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LastModified
2020年9月9日(水) 11:55:02
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三好 小文
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堤 理恵
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨 国際共著(徳島大学内研究者と国外研究機関所属研究者との共同研究)
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Shetty Abhishek
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Venkatesh Thejaswini
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. 堤 理恵([徳島大学.大学院医歯薬学研究部.医学域.栄養科学部門.医科栄養学系.代謝栄養学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Suresh Padmanaban S
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Gene expression changes and promoter methylation with the combined effects of estradiol and leptin in uterine tissue of the ovariectomized mice model of menopause.

副題 任意
要約 任意

(日) Substantial epidemiological studies have shown an association of obesity with the common gynecological malignancy, endometrial cancer. The relevant interactions and contribution of estradiol and the adipose cytokine, leptin, in endometrial lesions are not completely understood. Suitable animal models to understand the physiological response of uterine tissue to the combined effects of estradiol-leptin are lacking. To investigate the effect of estradiol-leptin crosstalk on gene expression and associated altered pathways, we established an ovariectomized mouse model, treated with 17-β estradiol (0.1 µg/mouse subcutaenously., for every 12 h) and/or recombinant mouse leptin (1 μg/g Bwt intraperitoneally., for every 12 h) for 4 h, 20 h, and 40 h. Gene expressions by semi-quantitative RT-PCR, uterine tissue protein phosphorylation status by western blotting and promoter methylation were analyzed in estradiol, progesterone insufficient animals. Semi-quantitative RT-PCR demonstrated significantly increased expression of Esr, Igf1, Igfbp3, Vegfr1, and Vegf, and significantly decreased expression of Mmp9 after co-treatment with estradiol and leptin, indicating a common transcriptional network regulated by the treatments. Ovariectomy-induced histomorphological changes were only reversed by estradiol. Methylation-specific PCR, analyzing methylation of CpG sites of Vegfa, Pgr, and Igf1, revealed that transcriptional regulation after hormonal treatments is independent of methylation at the examined CpG sites. Western blot confirmed the increased expression of PSTAT-3 (Ser-727) and PERK1/2 proteins after estradiol + leptin treatment, confirming the estradiol + leptin cross-talk hypothesis. In conclusion, our in vivo studies determined specific gene expression and signaling protein changes, and further unraveled the molecular targets of estradiol + leptin that may perturb endometrial homeostasis and lead to endometrial hyperplasia development in the chronic stimulated state.

キーワード 推奨
  1. (英) Animals
  2. (英) DNA Methylation
  3. (英) Drug Combinations
  4. (英) Endometrium
  5. (英) Estradiol
  6. (英) Female
  7. (英) Gene Expression Regulation
  8. (英) Leptin
  9. (英) Menopause
  10. (英) Mice
  11. (英) Models, Animal
  12. (英) Ovariectomy
  13. (英) Promoter Regions, Genetic
  14. (英) Uterus
発行所 推奨
誌名 必須 Molecular Biology Reports(Springer Netherlands)
(pISSN: 0301-4851, eISSN: 1573-4978)
ISSN 任意 1573-4978
ISSN: 0301-4851 (pISSN: 0301-4851, eISSN: 1573-4978)
Title: Molecular biology reports
Title(ISO): Mol Biol Rep
Supplier: Kluwer Online
Publisher: Springer Nature
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 47
必須 1
必須 151 168
都市 任意
年月日 必須 2019年 10月 10日
URL 任意
DOI 任意 10.1007/s11033-019-05116-8    (→Scopusで検索)
PMID 任意 31602590    (→Scopusで検索)
NAID 任意
WOS 任意
Scopus 任意 2-s2.0-85074054627
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) PublicationType: Journal Article