This Article Order Full text via Infotrieve Services 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 Nickoloff, B. J. Articles by Varani, J. Search for Related Content PubMed PubMed Citation Articles by Nickoloff, B. J. Articles by Varani, J.

American Journal of Pathology, Vol 132, 543-551, Copyright © 1988 by American Society for Investigative Pathology

REGULAR ARTICLES

Modulation of keratinocyte motility. Correlation with production of extracellular matrix molecules in response to growth promoting and antiproliferative factors

BJ Nickoloff, RS Mitra, BL Riser, VM Dixit and J Varani
Department of Pathology, University of Michigan, Medical School, Ann Arbor 48109-0602.

Normal human epidermal keratinocytes (KC) grown under conditions that maintain the undifferentiated state are highly motile. Migration of these cells as measured in two different assays (migration out of an agarose drop explant, and into micropore filters in a modified Boyden chamber), is stimulated by fibronectin (FN) and to a lesser extent by thrombospondin (TSP). In contrast, laminin (LN) inhibits KC migration. Cultivation of the cells for 1 day under conditions that induce differentiation (ie, in the presence of 1.4 mM Ca2+) suppresses KC motility. A number of soluble growth modulating polypeptide factors also influence KC migration. Transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) stimulate KC motility. These factors simultaneously induce KC production of FN and a significant portion of the stimulated motility can be inhibited with antibodies to FN. EGF and somatomedin-C (SM-C), but not TGF-beta, also stimulate TSP production while EGF and SM-C (but not TGF-beta) induce KC proliferation. In contrast to these factors, interferon-gamma (INF-gamma) inhibits KC production of both FN and TSP and concomitantly inhibits both motility and proliferation. These data suggest that KC properties essential for normal wound healing (ie, motility and proliferation) are regulated by both extracellular matrix molecules and soluble peptide factors. Finally, these effects of various growth promoting and antiproliferative factors on KCs may, in part, be mediated through alteration in the endogenous production of extracellular matrix molecules by KCs.

This article has been cited by other articles:

				A. I. Chernyavsky, J. Arredondo, L. M. Marubio, and S. A. Grando Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes J. Cell Sci., November 1, 2004; 117(23): 5665 - 5679. [Abstract] [Full Text] [PDF]

				A. I. Chernyavsky, J. Arredondo, J. Wess, E. Karlsson, and S. A. Grando Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors J. Cell Biol., July 19, 2004; 166(2): 261 - 272. [Abstract] [Full Text] [PDF]

				W. D. Hardie, D. R. Prows, G. D. Leikauf, and T. R. Korfhagen Attenuation of acute lung injury in transgenic mice expressing human transforming growth factor-alpha Am J Physiol Lung Cell Mol Physiol, November 1, 1999; 277(5): L1045 - L1050. [Abstract] [Full Text] [PDF]

				V. Chaturvedi, J.-Z. Qin, M. F. Denning, D. Choubey, M. O. Diaz, and B. J. Nickoloff Apoptosis in Proliferating, Senescent, and Immortalized Keratinocytes J. Biol. Chem., August 13, 1999; 274(33): 23358 - 23367. [Abstract] [Full Text] [PDF]

				Y. Berthiaume, O. Lesur, and A. Dagenais Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium Thorax, February 1, 1999; 54(2): 150 - 160. [Full Text]

				H. Chen, D. K. Strickland, and D. F. Mosher Metabolism of Thrombospondin 2. BINDING AND DEGRADATION BY 3T3 CELLS AND GLYCOSAMINOGLYCAN-VARIANT CHINESE HAMSTER OVARY CELLS J. Biol. Chem., July 5, 1996; 271(27): 15993 - 15999. [Abstract] [Full Text] [PDF]

				F van Ruissen, P. van Erp, G. de Jongh, J. Boezeman, P. van de Kerkhof, and J Schalkwijk Cell kinetic characterization of growth arrest in cultured human keratinocytes J. Cell Sci., January 8, 1994; 107(8): 2219 - 2228. [Abstract] [PDF]

				T. Tuan, L. Keller, D Sun, M. Nimni, and D Cheung Dermal fibroblasts activate keratinocyte outgrowth on collagen gels J. Cell Sci., January 8, 1994; 107(8): 2285 - 2289. [Abstract] [PDF]

				J. Adams and J Lawler Diverse mechanisms for cell attachment to platelet thrombospondin J. Cell Sci., January 4, 1993; 104(4): 1061 - 1071. [Abstract] [PDF]

				L. Strachan, J. G. Murison, R. L. Prestidge, M. A. Sleeman, J. D. Watson, and K. D. Kumble Cloning and Biological Activity of Epigen, a Novel Member of the Epidermal Growth Factor Superfamily J. Biol. Chem., May 18, 2001; 276(21): 18265 - 18271. [Abstract] [Full Text] [PDF]