TY - JOUR
T1 - Codominant regulation of keratin gene expression by cell surface receptors and nuclear receptors
AU - Tomić-Canić, Marjana
AU - Freedberg, Irwin M.
AU - Blumenberg, Miroslav
N1 - Funding Information:
We also thank E. Collado-Nunez for the synthetic oligonucleotides and J. Avins for secretarial help. Our research is supported by National Institutes of Health Grants AR30682, AR39176, AR40522, AR41850, and DK16636, and the NYU Skin Disease Research Center Grant AR39749. M.B. is a recipient of Irma T. Hirschl Career Scientist Award and M.T-C. is a recipient of the Ken Burdick Memorial Fellowship Award granted through the Dermatology Foundation.
PY - 1996/4/10
Y1 - 1996/4/10
N2 - 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 γ, TGFβ, 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 expression of appropriate genes in the treatment of human epidermal diseases.
AB - 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 γ, TGFβ, 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 expression of appropriate genes in the treatment of human epidermal diseases.
UR - http://www.scopus.com/inward/record.url?scp=17644441891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17644441891&partnerID=8YFLogxK
U2 - 10.1006/excr.1996.0115
DO - 10.1006/excr.1996.0115
M3 - Article
C2 - 8612697
AN - SCOPUS:17644441891
VL - 224
SP - 96
EP - 102
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -