Codominant regulation of keratin gene expression by cell surface receptors and nuclear receptors

Experimental Cell Research
M Tomic-CanicM Blumenberg

Abstract

Epidermal keratinocytes are subject to a large variety of signals that modulate their differentiation in health and their activation in disease. Hormones and vitamins, which act via nuclear receptors, affect the differentiation process, whereas growth factors and cytokines, which act via cell surface receptors, affect keratinocyte activation and related events. Using expression of keratin genes as markers for keratinocyte phenotype, we examined the interaction between the nuclear receptor and cell surface receptor pathways. We expected to find dominance of one of the pathways. Surprisingly, we found that the two pathways are codominant. Specifically, while EGF induces expression of K6 and K16 keratin genes, retinoic acid suppresses their expression, and when both mediators are present simultaneously, the level of expression is intermediate, a product of both signals. Similar codominant effects were found on other keratin genes using interferon gamma, TGF beta, and thyroid hormone signaling molecules. These codominant effects are specific only for genes that are regulated by both pathways. Our results suggest that a judicious combination of hormones, vitamins, growth factors, and cytokines may be used to target specific expressi...Continue Reading

Citations

Apr 3, 2004·Molecular and Cellular Biology·Nada RadojaMiroslav Blumenberg
Jun 23, 2006·Breast Cancer Research : BCR·Sandra L GrimmJeffrey M Rosen
Mar 11, 2011·The Journal of Investigative Dermatology·Yiwei ZhaoW H Irwin McLean
May 1, 2008·Clinical and Translational Science·Marjana Tomic-CanicMiroslav Blumenberg
Oct 12, 2007·The British Journal of Dermatology·N IshiuraK Tamaki
Apr 24, 2009·Journal of Cellular Physiology·Ding-Dar LeeMarjana Tomic-Canic
Jan 23, 2004·Endocrinology·Joshua D SaferMichael F Holick
Dec 12, 2012·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·F SchirraB Seitz

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