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HIF3A gene disruption causes abnormal alveoli structure and early neonatal death
https://asahikawa-med.repo.nii.ac.jp/records/2000588
https://asahikawa-med.repo.nii.ac.jp/records/20005884732eb21-9cc8-429b-856a-c6e37dda3b2b
| 名前 / ファイル | ライセンス | アクション |
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K604 Kawahata Tomoki_TD.pdf (4.4 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||||
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| 公開日 | 2025-11-19 | |||||||||||
| タイトル | ||||||||||||
| タイトル | HIF3A gene disruption causes abnormal alveoli structure and early neonatal death | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| その他（別言語等）のタイトル | ||||||||||||
| その他のタイトル | HIF3A遺伝子の破壊は肺胞構造異常と早期新生仔死亡を引き起こす | |||||||||||
| 言語 | ja | |||||||||||
| 著者 |
川幡, 智樹
× 川幡, 智樹
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| bibliographic_information |
en : PLoS One 巻 19, 号 5, p. e0300751, 発行日 2024-05-08 |
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| ISSN | ||||||||||||
| 収録物識別子タイプ | EISSN | |||||||||||
| 収録物識別子 | 1932-6203 | |||||||||||
| DOI | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0300751 | |||||||||||
| リンクURL | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0300751 | |||||||||||
| 言語 | en | |||||||||||
| dissertation_number | ||||||||||||
| 学位授与番号 | 甲第604号 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2024-09-30 | |||||||||||
| 学位名 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位名 | 博士（医学） | |||||||||||
| item_10_degree_grantor_32 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位授与機関名 | 旭川医科大学 | |||||||||||
| item_10_description_33 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Transcriptional response to changes in oxygen concentration is mainly controlled by hypoxia-inducible transcription factors (HIFs). Besides regulation of hypoxia-responsible gene expression, HIF-3α has recently been shown to be involved in lung development and in the metabolic process of fat tissue. However, the precise mechanism for such properties of HIF-3α is still largely unknown. To this end, we generated HIF3A gene-disrupted mice by means of genome editing technology to explore the pleiotropic role of HIF-3α in development and physiology. We obtained adult mice carrying homozygous HIF3A gene mutations with comparable body weight and height to wild-type mice. However, the number of litters and ratio of homozygous mutation carriers born from the mating between homozygous mutant mice was lower than expected due to sporadic deaths on postnatal day 1. HIF3A gene-disrupted mice exhibited abnormal configuration of the lung such as a reduced number of alveoli and thickened alveolar walls. Transcriptome analysis showed, as well as genes associated with lung development, an upregulation of stearoyl-Coenzyme A desaturase 1, a pivotal enzyme for fatty acid metabolism. Analysis of fatty acid composition in the lung employing gas chromatography indicated an elevation in palmitoleic acid and a reduction in oleic acid, suggesting an imbalance in distribution of fatty acid, a constituent of lung surfactant. Accordingly, administration of glucocorticoid injections during pregnancy resulted in a restoration of normal alveolar counts and a decrease in neonatal mortality. In conclusion, these observations provide novel insights into a pivotal role of HIF-3α in the preservation of critically important structure and function of alveoli beyond the regulation of hypoxia-mediated gene expression. | |||||||||||
| 言語 | en | |||||||||||
| item_10_description_36 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | Copyright: © 2024 Kawahata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||||||||
| 言語 | en | |||||||||||
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| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
