Loss of epidermal hypoxia-inducible factor-1α accelerates epidermal aging and affects re-epithelialization in human and mouse

Author:

Rezvani Hamid Reza12,Ali Nsrein12,Serrano-Sanchez Martin12,Dubus Pierre3,Varon Christine45,Ged Cécile12,Pain Catherine12,Cario-André Muriel126,Seneschal Julien126,Taïeb Alain126,de Verneuil Hubert12,Mazurier Frédéric12

Affiliation:

1. INSERM, Biothérapies des maladies génétiques et cancers, U1035, 146 rue Léo Saignat, Bordeaux, F-33000 France

2. Université Bordeaux, Biothérapies des maladies génétiques et cancers, U1035, 146 rue Léo Saignat, Bordeaux, F-33000 France

3. Université Bordeaux, Histologie et pathologie moléculaire des tumeurs, EA 2406, 146 rue Léo Saignat, Bordeaux, F-33000 France

4. INSERM, Laboratoire de bactériologie, U853, 146 rue Léo Saignat, Bordeaux, F-33000 France

5. Université Bordeaux, Laboratoire de bactériologie, U853, 146 rue Léo Saignat, BordeauxF-33000 France

6. CHU de Bordeaux, Département de Dermatologie & Dermatologie Pédiatrique, Centre de référence des maladies rares de la peau, Hôpital St André, 1, rue Jean Burguet, Bordeaux, F-33000 France

Abstract

In mouse and human skin, HIF-1α is constitutively expressed in the epidermis, mainly in the basal layer. HIF-1α has been shown to have crucial systemic functions: regulation of kidney erythropoietin production in mice with constitutive HIF-1α epidermal deletion, and hypervascularity following epidermal HIF-1α overexpression. However, its local role in keratinocyte physiology has not been clearly defined. To address the function of HIF-1α in the epidermis, we used the mouse model of HIF-1α knockout targeted to keratinocytes (K14-Cre/Hif1aflox/flox). These mice had a delayed skin phenotype characterized by skin atrophy and pruritic inflammation, partly mediated by basement membrane disturbances involving laminin-332 (Ln-332) and integrins. We also investigated the relevance of results of studies in mice to human skin using reconstructed epidermis and showed that HIF-1α knockdown in human keratinocytes impairs the formation of a viable reconstructed epidermis. A diminution of keratinocyte growth potential, following HIF-1α silencing, was associated with a decreased expression of Ln-322 and α6 integrin and β1 integrin. Overall, these results indicate a role of HIF-1α in skin homeostasis especially during epidermal aging.

Publisher

The Company of Biologists

Subject

Cell Biology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3