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Inactivation of autophagy leads to changes in sebaceous gland morphology and function
Author(s) -
Rossiter Heidemarie,
Stübiger Gerald,
Gröger Marion,
König Ulrich,
Gruber Florian,
Sukseree Supawadee,
Mlitz Veronika,
Buchberger Maria,
Oskolkova Olga,
Bochkov Valery,
Eckhart Leopold,
Tschachler Erwin
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13752
Subject(s) - keratin , sebaceous gland , mutant , autophagy , epidermis (zoology) , chemistry , medicine , endocrinology , lipid droplet , keratin 14 , phenotype , biology , biochemistry , microbiology and biotechnology , transgene , gene , genetically modified mouse , anatomy , genetics , apoptosis
We have reported recently that inactivation of the essential autophagy‐related gene 7 ( Atg7) in keratinocytes has little or no impact on morphology and function of the epidermal barrier in experimental animals. When these mice aged, mutant males, ( Atg7 Δ KC ), developed an oily coat. As the keratin 14 promoter driven cre/LoxP system inactivates floxed Atg7 in all keratin 14 (K14) expressing cells, including sebocytes, we investigated whether the oily hair phenotype was the consequence of changes in function of the skin sebaceous glands. Using an antibody to the GFP ‐ LC 3 fusion protein, autophagosomes were detected at the border of sebocyte disintegration in control but not in mutant animals, suggesting that autophagy was (a) active in normal sebaceous glands and (b) was inactivated in the mutant mice. Detailed analysis established that dorsal sebaceous glands were about twice as large in all Atg7 Δ KC mice compared to those of controls ( Atg7 F/F), and their rate of sebocyte proliferation was increased. In addition, male mutant mice yielded twice as much lipid per unit hair as age‐matched controls. Analysis of sebum lipids by thin layer chromatography revealed a 40% reduction in the proportion of free fatty acids ( FFA ) and cholesterol, and a 5‐fold increase in the proportion of fatty acid methyl esters ( FAME ). In addition, the most common diester wax species (58‐60 carbon atoms) were increased, while shorter species (54‐55 carbon atoms) were under‐represented in mutant sebum. Our data show that autophagy contributes to sebaceous gland function and to the control of sebum composition.