Autophagy induction regulates aquaporin 3-mediated skin fibroblast ageing*
H. Xie
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008 China
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, Hunan, 410008 China
Search for more papers by this authorL. Zhou
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal)
Search for more papers by this authorF. Liu
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Funding acquisition (equal), Investigation (equal)
Search for more papers by this authorJ. Long
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal)
Search for more papers by this authorS. Yan
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal)
Search for more papers by this authorY. Xie
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Search for more papers by this authorCorresponding Author
X. Hu
Department of Infectious Diseases, Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 China
Correspondence
Ji Li; Xingwang Hu.
Email: [email protected]; [email protected]
Contribution: Conceptualization (lead), Data curation (equal), Funding acquisition (supporting), Methodology (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorCorresponding Author
J. Li
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008 China
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, Hunan, 410008 China
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 China
Department of Dermatology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830092 China
Correspondence
Ji Li; Xingwang Hu.
Email: [email protected]; [email protected]
Search for more papers by this authorH. Xie
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008 China
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, Hunan, 410008 China
Search for more papers by this authorL. Zhou
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal)
Search for more papers by this authorF. Liu
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Funding acquisition (equal), Investigation (equal)
Search for more papers by this authorJ. Long
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal)
Search for more papers by this authorS. Yan
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal)
Search for more papers by this authorY. Xie
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Search for more papers by this authorCorresponding Author
X. Hu
Department of Infectious Diseases, Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 China
Correspondence
Ji Li; Xingwang Hu.
Email: [email protected]; [email protected]
Contribution: Conceptualization (lead), Data curation (equal), Funding acquisition (supporting), Methodology (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorCorresponding Author
J. Li
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008 China
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008 China
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, Hunan, 410008 China
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 China
Department of Dermatology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830092 China
Correspondence
Ji Li; Xingwang Hu.
Email: [email protected]; [email protected]
Search for more papers by this authorPlain language summary available online
Summary
Background
Long- and short-term ultraviolet (UV) exposure have distinct biological effects on human fibroblasts.
Objectives
To elucidate the underlying mechanisms of the biological effects of UV exposure on human skin fibroblasts.
Methods
We subjected human skin fibroblast cells with or without aquaporin 3 (AQP3), death effector domain-containing protein (DEDD) or Beclin1 manipulation to UVA treatment and evaluated autophagy and senescence in them.
Results
Short-term UVA irradiation induced autophagy and upregulated AQP3 but not senescence, whereas long-term UVA irradiation inhibited autophagy, AQP3 and trigger senescence in vitro and in vivo. Silencing AQP3 abolished short-term UVA irradiation-induced autophagy and led to cellular senescence, whereas AQP3 overexpression partially rescued the senescence and autophagy inhibition induced by long-term UVA exposure in vitro. Mechanistically, the transcription factor Jun was found to bind to the AQP3 promoter to activate its transcription following short-term UVA exposure. Subsequently, AQP3 interacted with DEDD to induce its ubiquitination-mediated degradation and promote autophagy, and bound to Beclin1 to directly activate autophagy. Finally, autophagy induced by AQP3 overexpression robustly prevented UVA-induced senescence in vitro and in vivo.
Conclusions
Our study indicates that AQP3 controls skin fibroblast photoageing by regulating autophagy and represents a potential target for future interventions against skin ageing.
Supporting Information
| Filename | Description |
|---|---|
| bjd20662-sup-0001-AppendixS1.docxWord 2007 document , 17.2 KB | Appendix S1 Supplementary methodology. |
| bjd20662-sup-0002-TableS1.docxWord 2007 document , 15.5 KB | Table S1 Primers sequences used in this study. |
| bjd20662-sup-0003-FigureS1.tifTIFF image, 50.4 MB | Figure S1 Ultraviolet A-induced autophagy in HaCaT cells, normal human skin fibroblasts and mouse tissue. |
| bjd20662-sup-0004-FigureS2.tifTIFF image, 47.5 MB | Figure S2 Aquaporin 3 and death effector domain-containing protein (DEDD) colocalization in HaCaT cells. |
| bjd20662-sup-0005-FigureS3.tifTIFF image, 33.6 MB | Figure S3 Interactions between aquaporin 3, death effector domain-containing protein (DEDD) and Beclin1. |
| bjd20662-sup-0006-FigureS4.tifTIFF image, 16.5 MB | Figure S4 Verification of aquaporin 3−/− knockout mice. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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