Universität zu Köln

Skazik, Claudia, Amann, Philipp M., Heise, Ruth, Marquardt, Yvonne, Czaja, Katharina, Kim, Arianna, Ruehl, Ralph, Kurschat, Peter, Merk, Hans F., Bickers, David R. and Baron, Jens M. (2014). Downregulation of STRA6 Expression in Epidermal Keratinocytes Leads to Hyperproliferation-Associated Differentiation in Both In Vitro and In Vivo Skin Models. J. Invest. Dermatol., 134 (6). S. 1579 - 1589. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Retinoids are known to affect skin cell proliferation and differentiation and are key molecules that target retinoid and retinoic acid receptors (RXRs and RARs), leading to physiological and pharmacologic effects. Our aim was to elucidate the role of the retinol-binding protein receptor STRA6, mediating cellular uptake of retinol, on skin structure and function. Our results indicate that STRA6 is constitutively expressed in human epidermal keratinocytes and dermal fibroblasts and is regulated via RAR/RXR-mediated pathways. HaCaT (Human adult low Calcium high Temperature) cells with stable STRA6 knockdown (STRA6KD) showed increased proliferation. Consistently, human organotypic 3D skin models using stable STRA6KD HaCaT cells showed a significantly thicker epidermis and enhanced expression of activation, differentiation, and proliferation markers. The effects were reversible after treatment with free retinol. Human skin reconstitution employing STRA6KD HaCaT cells leads to massive epithelial thickening under in vivo conditions in SCID mice. We propose that STRA6KD could lead to cellular vitamin A deficiency in keratinocytes. Consequently, STRA6 has a role for regulating retinoid homeostasis and in helping to program signaling that drives proliferation and differentiation of human skin cells. By its influence on hyperproliferation-associated differentiation, STRA6 could also have a role in skin regeneration and could be a target for pharmacological approaches to improve wound healing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Skazik, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Amann, Philipp M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heise, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Marquardt, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Czaja, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Arianna UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruehl, Ralph UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurschat, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Merk, Hans F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bickers, David R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baron, Jens M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-437196
DOI:	10.1038/jid.2013.507
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	134
Number:	6
Page Range:	S. 1579 - 1589
Date:	2014
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETINOL-BINDING-PROTEIN; CELL-SURFACE-RECEPTOR; VITAMIN-A METABOLISM; MEMBRANE-RECEPTOR; ACID; GENE; ACYLTRANSFERASE; PROLIFERATION; HOMEOSTASIS; INDUCTION Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43719