Publication: Epidermal keratinocytes form a functional skin barrier in the absence of Atg7 dependent autophagy
0
0
Issued Date
2013
Resource Type
File Type
application/pdf
ISSN
9231811
Other identifier(s)
2-s2.0-84879031086
Rights Holder(s)
Scopus
Bibliographic Citation
Journal of Dermatological Science. Vol 71, No.1 (2013), p.67-75
Suggested Citation
Rossiter H., König U., Barresi C., Buchberger M., Ghannadan M., Zhang C.-F., Mlitz V., Gmeiner R., Sukseree S., Födinger D., Eckhart L., Tschachler E. Epidermal keratinocytes form a functional skin barrier in the absence of Atg7 dependent autophagy. Journal of Dermatological Science. Vol 71, No.1 (2013), p.67-75. doi:10.1016/j.jdermsci.2013.04.015 Retrieved from: https://hdl.handle.net/20.500.14740/6631
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 (Atg7epi 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 Atg7epi epidermis. Atg7epi 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 Atg7epi mice. Conclusion: This study demonstrates that autophagy is constitutively active in the epidermis but not essential for the barrier function of the skin. © 2013 Japanese Society for Investigative Dermatology.
Subject(s)
Cell protein
Animal cell
Animal tissue
Article
Autophagosome
Autophagy
Autophagy associated gene 7
Cell function
Controlled study
Epidermis
Gene
Gene inactivation
Histology
Keratinocyte
Membrane formation
Mouse
Nonhuman
Priority journal
Skin function
Skin structure
Skin water loss
Western blotting
Animals
Autophagy
Cell Differentiation
Cells, Cultured
Diffusion
Epidermis
Green Fluorescent Proteins
Keratin-14
Keratinocytes
Mice
Mice, Inbred CBA
Mice, Knockout
Mice, Transgenic
Microtubule-Associated Proteins
Permeability
Promoter Regions, Genetic
Skin Absorption
Water Loss, Insensible
Animal cell
Animal tissue
Article
Autophagosome
Autophagy
Autophagy associated gene 7
Cell function
Controlled study
Epidermis
Gene
Gene inactivation
Histology
Keratinocyte
Membrane formation
Mouse
Nonhuman
Priority journal
Skin function
Skin structure
Skin water loss
Western blotting
Animals
Autophagy
Cell Differentiation
Cells, Cultured
Diffusion
Epidermis
Green Fluorescent Proteins
Keratin-14
Keratinocytes
Mice
Mice, Inbred CBA
Mice, Knockout
Mice, Transgenic
Microtubule-Associated Proteins
Permeability
Promoter Regions, Genetic
Skin Absorption
Water Loss, Insensible