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J Dermatol Sci. 2013 Jul;71(1):67-75. doi: 10.1016/j.jdermsci.2013.04.015. Epub 2013 Apr 19.

Epidermal keratinocytes form a functional skin barrier in the absence of Atg7 dependent autophagy.

Author information

1
Department of Dermatology, Medical University of Vienna, Austria.

Abstract

BACKGROUND:

Cornification of keratinocytes involves the degradation of intracellular constituents which has led to the hypothesis that autophagy plays a role in this process. Mice, in which essential autophagy-related genes such as Atg7 are deleted systemically, die after birth and have not been characterized for potential epidermal defects.

OBJECTIVE:

This study tested whether autophagy is essential for epidermal barrier formation and function.

METHODS:

Atg7 was inactivated in epidermal keratinocytes by the Cre-loxP system under the control of the keratin K14 promoter (Atg7Δepi mice). Autophagic activity was detected using the GFP-microtubule-associated protein light chain 3 (GFP-LC3) reporter construct and Western blot analysis of LC3. Epidermal morphology was examined by histological and ultrastructural analyses, and barrier functions were assessed by dye diffusion and water loss assays.

RESULTS:

Suprabasal epidermal cells of normal mice contained GFP-LC3-labeled autophagosomes and epidermal lysates of these mice showed an excess of lipidated over non-lipidated LC3. These features of active autophagy were efficiently suppressed in Atg7Δepi epidermis. Atg7Δepi mice survived the perinatal period and were apparently healthy. Histologically, their epidermis was inconspicuous and ultrastructural analysis revealed no significant defect in cornification. There was however, an increase in the thickness of corneocytes in the back skin of mutant mice. Nevertheless, resistance to dye penetration into the skin and transepidermal water loss were normal in Atg7Δepi mice.

CONCLUSION:

This study demonstrates that autophagy is constitutively active in the epidermis but not essential for the barrier function of the skin.

PMID:
23669018
DOI:
10.1016/j.jdermsci.2013.04.015
[Indexed for MEDLINE]

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