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タイトル: | Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction |
著者: | Sasaki, Lena Hamada, Yuki Yarimizu, Daisuke Suzuki, Tomo Nakamura, Hiroki Shimada, Aya Pham, Khanh Tien Nguyen Shao, Xinyan Yamamura, Koki Inatomi, Tsutomu Morinaga, Hironobu Nishimura, Emi K. Kudo, Fujimi Manabe, Ichiro Haraguchi, Shogo Sugiura, Yuki Suematsu, Makoto Kinoshita, Shigeru Machida, Mamiko Nakajima, Takeshi Kiyonari, Hiroshi Okamura, Hitoshi Yamaguchi, Yoshiaki https://orcid.org/0000-0003-4126-542X (unconfirmed) Miyake, Takahito https://orcid.org/0000-0002-4356-5883 (unconfirmed) Doi, Masao https://orcid.org/0000-0001-6264-9217 (unconfirmed) |
著者名の別形: | 佐々木, 玲奈 濵田, 悠貴 鑓水, 大介 鈴木, 智 中村, 洋貴 島田, 彩 山村, 公基 稲冨, 勉 森永, 浩伸 西村, 栄美 工藤, 藤美 真鍋, 一郎 原口, 省吾 杉浦, 悠毅 末松, 誠 木下, 茂 町田, 麻実子 中嶋, 毅 清成, 寛 岡村, 均 山口, 賀章 三宅, 崇仁 土居, 雅夫 |
キーワード: | Ageing Endocrine system and metabolic diseases |
発行日: | Feb-2022 |
出版者: | Springer Nature |
誌名: | Nature Aging |
巻: | 2 |
号: | 2 |
開始ページ: | 105 |
終了ページ: | 114 |
抄録: | Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction. |
記述: | 新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14. Mutant mice shed no tears: Kyoto University shows dry-eye disorder improved by modulating hormone levels. 京都大学プレスリリース. 2022-03-10. |
著作権等: | © The Author(s) 2022 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. |
URI: | http://hdl.handle.net/2433/267987 |
DOI(出版社版): | 10.1038/s43587-021-00167-8 |
PubMed ID: | 37117756 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2022-02-14 https://www.kyoto-u.ac.jp/en/research-news/2022-03-10 |
出現コレクション: | 学術雑誌掲載論文等 |
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