Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction
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- Sasaki, Lena
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Hamada, Yuki
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Yarimizu, Daisuke
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Suzuki, Tomo
- Department of Ophthalmology, Kyoto Prefectural University of Medicine; Department of Ophthalmology, Kyoto City Hospital
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- Nakamura, Hiroki
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Shimada, Aya
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Pham, Khanh Tien Nguyen
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Shao, Xinyan
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Yamamura, Koki
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Inatomi, Tsutomu
- Department of Ophthalmology, National Center for Geriatrics and Gerontology
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- Morinaga, Hironobu
- Dpartment of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University
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- Nishimura, Emi K.
- Dpartment of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University
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- Kudo, Fujimi
- Department of Disease Biology and Molecular Medicine, Graduate School of Medicine, Chiba University
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- Manabe, Ichiro
- Department of Disease Biology and Molecular Medicine, Graduate School of Medicine, Chiba University
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- Haraguchi, Shogo
- Department of Biochemistry, Showa University School of Medicine
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- Sugiura, Yuki
- Department of Biochemistry, Keio University School of Medicine
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- Suematsu, Makoto
- Department of Biochemistry, Keio University School of Medicine
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- Kinoshita, Shigeru
- Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine
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- Machida, Mamiko
- Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Co.
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- Nakajima, Takeshi
- Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Co.
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- Kiyonari, Hiroshi
- Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research
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- Okamura, Hitoshi
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University; Division of Physiology and Neurobiology, Graduate School of Medicine, Kyoto University
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- Yamaguchi, Yoshiaki
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Miyake, Takahito
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Doi, Masao
- Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University
Abstract
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.
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.
Journal
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- Nature Aging
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Nature Aging 2 (2), 105-114, 2022-02
Springer Nature
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Details 詳細情報について
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- CRID
- 1050009683079817216
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- NII Article ID
- 120007191374
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- ISSN
- 26628465
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- HANDLE
- 2433/267987
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN