HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hanley, K. Articles by Feingold, K. R. Search for Related Content PubMed PubMed Citation Articles by Hanley, K. Articles by Feingold, K. R. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 42, 390-398, March 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D

Correspondence to: Kenneth R. Feingold, at the Metabolism Section (111F), Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121.

Lipids that are synthesized de novo in the epidermis, including fatty acids, oxysterols, 1,25-dihydroxyvitamin D₃, and farnesol, can regulate the differentiation of normal human keratinocytes (NHK). Cholesterol sulfate (CS), an epidermal lipid that is produced in the upper nucleated layers of the epidermis coincident with terminal differentiation, has been shown to play a role in the regulation of the late stages of keratinocyte differentiation, including formation of the cornified envelope. In the present study, we determined i) whether CS regulates involucrin (INV), an early keratinocyte differentiation marker, and ii) the mechanism by which CS regulates differentiation. mRNA and protein levels of INV, a precursor protein of the cornified envelope, increased 2- to 3-fold in NHK incubated in the presence of CS. In contrast, cholesterol had no effect on INV protein or mRNA levels. Transcriptional regulation was assessed in NHK transfected with INV promoter-luciferase constructs. CS increased luciferase reporter activity approximately 2- to 3-fold in NHK transfected with a 3.7-kb INV promoter construct. Deletional analysis revealed a CS-responsive region of the INV promoter located between bp -2452 and -1880. A 5-base pair (bp) mutation of the AP-1 site (bp -2117 to -2111) within this responsive region abolished CS responsiveness, suggesting a role for the AP-1 complex in the regulation of INV transcription by CS. Electrophoretic mobility shift analysis demonstrated increased binding of nuclear extracts isolated from CS-treated NHK to AP-1 DNA as compared with vehicle-treated controls. Incubation of the nuclear extract with the appropriate antibodies showed that the AP-1 DNA-binding complex contained Fra-1, Fra-2, and Jun D. Western blots demonstrated that CS treatment increased the levels of Fra-1, Fra-2, and Jun D, and Northern analyses revealed that CS increased mRNA levels for these same AP-1 factors.

These data indicate that CS, an endogenous lipid synthesized by keratinocytes, regulates the early stages of keratinocyte differentiation, and may do so through its ability to modulate levels of AP-1 proteins. — Hanley, K., L. Wood, D. C. Ng, S. S. He, P. Lau, A. Moser, P. M. Elias, D. D. Bikle, M. L. Williams, and K. R. Feingold. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J. Lipid Res. 2001. 42: 390;–398.

Supplementary key words: transglutaminase, cornified envelope, differentiation, AP-1

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. M. Elias, M. L. Williams, W. M. Holleran, Y. J. Jiang, and M. Schmuth Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism J. Lipid Res., April 1, 2008; 49(4): 697 - 714. [Abstract] [Full Text] [PDF]

				K. R. Feingold Thematic review series: Skin Lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis J. Lipid Res., December 1, 2007; 48(12): 2531 - 2546. [Abstract] [Full Text] [PDF]

				Y. J. Jiang, B. Lu, P. Kim, P. M. Elias, and K. R. Feingold Regulation of ABCA1 expression in human keratinocytes and murine epidermis J. Lipid Res., October 1, 2006; 47(10): 2248 - 2258. [Abstract] [Full Text] [PDF]

				Y. J. Jiang, P. Kim, P. M. Elias, and K. R. Feingold LXR and PPAR activators stimulate cholesterol sulfotransferase type 2 isoform 1b in human keratinocytes J. Lipid Res., December 1, 2005; 46(12): 2657 - 2666. [Abstract] [Full Text] [PDF]

				J. Kallen, J.-M. Schlaeppi, F. Bitsch, I. Delhon, and B. Fournier Crystal Structure of the Human ROR{alpha} Ligand Binding Domain in Complex with Cholesterol Sulfate at 2.2 A J. Biol. Chem., April 2, 2004; 279(14): 14033 - 14038. [Abstract] [Full Text] [PDF]

				K. A. Lee, H. Fuda, Y. C. Lee, M. Negishi, C. A. Strott, and L. C. Pedersen Crystal Structure of Human Cholesterol Sulfotransferase (SULT2B1b) in the Presence of Pregnenolone and 3'-Phosphoadenosine 5'-Phosphate: RATIONALE FOR SPECIFICITY DIFFERENCES BETWEEN PROTOTYPICAL SULT2A1 AND THE SULT2B1 ISOFORMS J. Biol. Chem., November 7, 2003; 278(45): 44593 - 44599. [Abstract] [Full Text] [PDF]

				C. A. Strott and Y. Higashi Cholesterol sulfate in human physiology: what's it all about? J. Lipid Res., July 1, 2003; 44(7): 1268 - 1278. [Abstract] [Full Text] [PDF]

				C. Shimizu, H. Fuda, H. Yanai, and C. A. Strott Conservation of the Hydroxysteroid Sulfotransferase SULT2B1 Gene Structure in the Mouse: Pre- and Postnatal Expression, Kinetic Analysis of Isoforms, and Comparison with Prototypical SULT2A1 Endocrinology, April 1, 2003; 144(4): 1186 - 1193. [Abstract] [Full Text] [PDF]

				C. A. Strott Sulfonation and Molecular Action Endocr. Rev., October 1, 2002; 23(5): 703 - 732. [Abstract] [Full Text] [PDF]

				H. Fuda, Y. C. Lee, C. Shimizu, N. B. Javitt, and C. A. Strott Mutational Analysis of Human Hydroxysteroid Sulfotransferase SULT2B1 Isoforms Reveals That Exon 1B of the SULT2B1 Gene Produces Cholesterol Sulfotransferase, whereas Exon 1A Yields Pregnenolone Sulfotransferase J. Biol. Chem., September 20, 2002; 277(39): 36161 - 36166. [Abstract] [Full Text] [PDF]