QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 27 May 2003
doi: 10.1242/jcs.00474

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.00474v1 116/14/2937    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maas-Szabowski, N. Articles by Fusenig, N. E. Search for Related Content PubMed PubMed Citation Articles by Maas-Szabowski, N. Articles by Fusenig, N. E.

Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-

Division of Differentiation and Carcinogenesis (B0600), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

^* Author for correspondence (e-mail: n.fusenig{at}dkfz.de)

Accepted 11 March 2003

The human keratinocyte cell line HaCaT expresses essentially all epidermal differentiation markers but exhibits deficiencies in tissue organization as surface transplants in nude mice and even more so in organotypic co-cultures with fibroblasts. Whereas tissue differentiation by normal keratinocytes (NEKs) is regulated by stromal interactions, this mechanism is impaired in HaCaT cells. This regulatory process is initiated by interleukin-1 (IL-1) release in keratinocytes, which induces expression of keratinocyte growth factor (KGF/FGF-7) and granulocyte macrophage-colony stimulating factor (GM-CSF) in fibroblasts. Production and release of IL-1 is very low and, consequently, expression of the fibroblast-derived growth factors KGF/FGF-7 and GM-CSF is absent in HaCaT-fibroblast co-cultures. However, addition of KGF and GMCSF, respectively, is inefficient to improve stratification and differentiation by HaCaT cells due to the low expression of their cognate receptors. More importantly, expression and release of the autocrine keratinocyte growth factor TGF- is dramatically decreased in HaCaT cells. Addition of TGF- or EGF stimulated HaCaT cell proliferation but, even more effectively, suppressed apoptosis, thus facilitating the formation of a regularly stratified epithelium. Furthermore, TGF- enhanced the expression of the receptors for KGF and GM-CSF so that addition of these growth factors, or of their inducer IL-1, further improved epidermal tissue differentiation leading to in vitro skin equivalents comparable with cultures of NEKs. Thus, supplementing TGF- normalized epidermal tissue regeneration by immortal HaCaT keratinocytes and their interaction with stromal cells so that regular skin equivalents are produced as standardized in vitro models.

Key words: HaCaT, Keratinocytes, Skin equivalent, Epithelial-mesenchymal interaction, Cytokines

This article has been cited by other articles:

				S. Muffler, H.-J. Stark, M. Amoros, B. Falkowska-Hansen, K. Boehnke, H.-J. Buhring, A. Marme, J. R. Bickenbach, and P. Boukamp A Stable Niche Supports Long-Term Maintenance of Human Epidermal Stem Cells in Organotypic Cultures Stem Cells, October 1, 2008; 26(10): 2506 - 2515. [Abstract] [Full Text] [PDF]

				L. Crigler, A. Kazhanie, T.-J. Yoon, J. Zakhari, J. Anders, B. Taylor, and V. M. Virador Isolation of a mesenchymal cell population from murine dermis that contains progenitors of multiple cell lineages FASEB J, July 1, 2007; 21(9): 2050 - 2063. [Abstract] [Full Text] [PDF]

				S. Pankow, C. Bamberger, A. Klippel, and S. Werner Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase J. Cell Sci., October 1, 2006; 119(19): 4033 - 4046. [Abstract] [Full Text] [PDF]

				I. Sher, S. Zisman-Rozen, L. Eliahu, J. M. Whitelock, N. Maas-Szabowski, Y. Yamada, D. Breitkreutz, N. E. Fusenig, E. Arikawa-Hirasawa, R. V. Iozzo, et al. Targeting Perlecan in Human Keratinocytes Reveals Novel Roles for Perlecan in Epidermal Formation J. Biol. Chem., February 24, 2006; 281(8): 5178 - 5187. [Abstract] [Full Text] [PDF]

				O. G. Rossler and G. Thiel Brain-derived neurotrophic factor-, epidermal growth factor-, or A-Raf-induced growth of HaCaT keratinocytes requires extracellular signal-regulated kinase Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1118 - C1129. [Abstract] [Full Text] [PDF]