Grond_2017_J.Invest.Dermatol_137_403

Reference

Title : Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation - Grond_2017_J.Invest.Dermatol_137_403
Author(s) : Grond S , Radner FP , Eichmann TO , Kolb D , Grabner GF , Wolinski H , Gruber R , Hofer P , Heier C , Schauer S , Rulicke T , Hoefler G , Schmuth M , Elias PM , Lass A , Zechner R , Haemmerle G
Ref : Journal of Investigative Dermatology , 137 :403 , 2017
Abstract :

Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired omega-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for omega-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in omega-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism.

PubMedSearch : Grond_2017_J.Invest.Dermatol_137_403
PubMedID: 27725204
Gene_locus related to this paper: human-ABHD5

Related information

Gene_locus human-ABHD5

Citations formats

Grond S, Radner FP, Eichmann TO, Kolb D, Grabner GF, Wolinski H, Gruber R, Hofer P, Heier C, Schauer S, Rulicke T, Hoefler G, Schmuth M, Elias PM, Lass A, Zechner R, Haemmerle G (2017)
Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation
Journal of Investigative Dermatology 137 :403

Grond S, Radner FP, Eichmann TO, Kolb D, Grabner GF, Wolinski H, Gruber R, Hofer P, Heier C, Schauer S, Rulicke T, Hoefler G, Schmuth M, Elias PM, Lass A, Zechner R, Haemmerle G (2017)
Journal of Investigative Dermatology 137 :403