| First Author | Grond S | Year | 2017 |
| Journal | J Invest Dermatol | Volume | 137 |
| Issue | 2 | Pages | 403-413 |
| PubMed ID | 27725204 | Mgi Jnum | J:240055 |
| Mgi Id | MGI:5882271 | Doi | 10.1016/j.jid.2016.09.025 |
| Citation | Grond S, et al. (2017) Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation. J Invest Dermatol 137(2):403-413 |
| abstractText | 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. |
