AMPK Inhibits mTOR-Driven Keratinocyte Proliferation after Skin Damage and Stress
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..
Epidermal keratinocytes (KCs) rapidly proliferate to repair the skin barrier, and a strict control of division is necessary for healthy tissue homeostasis. However, the pathways that restrain proliferation after epidermal stress are not known. AMPK is an important signaling mediator of energy metabolism previously associated with skin stress and cancer; yet, its explicit impact on KC growth is not known. To examine the requirement of epidermal AMPK in physiologic skin repair, we genetically deleted AMPK within all adult, keratin 14‒expressing KCs of mice. AMPK loss resulted in hyperproliferation and hyperactive mTOR signaling after acute wounding, UVB exposure, and phorbol ester application. This excessive division could be completely blocked by the mTORC1 inhibitor rapamycin. Moreover, we establish that the diabetes drug metformin depends on AMPK to suppress stress-induced KC proliferation. Collectively, these findings show that KC AMPK restrains mTORC1 to control epidermal proliferation after tissue injury.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:141 |
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| Enthalten in: |
The Journal of investigative dermatology - 141(2021), 9 vom: 10. Sept., Seite 2170-2177.e3 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Crane, Elizabeth D [VerfasserIn] |
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| Links: |
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| Themen: |
9100L32L2N |
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| Anmerkungen: |
Date Completed 13.12.2021 Date Revised 14.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jid.2020.12.036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322978394 |
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| 520 | |a Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Epidermal keratinocytes (KCs) rapidly proliferate to repair the skin barrier, and a strict control of division is necessary for healthy tissue homeostasis. However, the pathways that restrain proliferation after epidermal stress are not known. AMPK is an important signaling mediator of energy metabolism previously associated with skin stress and cancer; yet, its explicit impact on KC growth is not known. To examine the requirement of epidermal AMPK in physiologic skin repair, we genetically deleted AMPK within all adult, keratin 14‒expressing KCs of mice. AMPK loss resulted in hyperproliferation and hyperactive mTOR signaling after acute wounding, UVB exposure, and phorbol ester application. This excessive division could be completely blocked by the mTORC1 inhibitor rapamycin. Moreover, we establish that the diabetes drug metformin depends on AMPK to suppress stress-induced KC proliferation. Collectively, these findings show that KC AMPK restrains mTORC1 to control epidermal proliferation after tissue injury | ||
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| 700 | 1 | |a Zhang, Hui |e verfasserin |4 aut | |
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