Loss of keratin 10 is accompanied by increased sebocyte proliferation and differentiation.
Here, we present strong evidence that the targeted deletion of keratin 10 (K10) alters sebocyte differentiation in mice, mediated by an increased proliferation and differentiation of cells located in the periphery of the glands. This was not accompanied by the induction of the proliferation-associated keratins K6, K16 and K17. Sebaceous gland cells of K10-/- mice showed an accelerated turnover and secreted more sebum including wax esters, triglycerides, and cholesterol esters. The levels of the major epidermal lipids ceramides and cholesterol were also increased, whereas glycosylceramides and sphingomyelin were decreased which was not based on altered sphingolipid biosynthesis. The amount of Cer(OS), covalently bound to the cornified envelope, remained unchanged, as well as the amount of loricrin and involucrin. In agreement with the unaltered expression of beta-catenin and its targets cyclin D1 and c-Myc, we conclude that the altered composition of the suprabasal intermediate filament cytoskeleton in K10-/- mice increased the differentiation of epidermal stem cells towards the sebocyte lineage.
Reichelt
Julia
J
Institut für Physiologische Chemie, Universität Bonn, Bonn, Germany. j.reichelt@uni-bonn.de
Breiden
Bernadette
B
Sandhoff
Konrad
K
Magin
Thomas M
TM
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002518:Ceramides / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism; D017353:Gene Deletion; D018390:Gene Targeting; D053550:Keratin-10; D007633:Keratins / Q000235:genetics* / Q000502:physiology*; D008055:Lipids / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism; D012629:Sebum / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D002518:Ceramides; D003598:Cytoskeletal Proteins; C507491:Krt10 protein, mouse; D008055:Lipids; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D051176:beta Catenin; D053550:Keratin-10; D007633:Keratins