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