+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Retinoid regulation of heparin-binding EGF-like growth factor gene expression in human keratinocytes and skin



Retinoid regulation of heparin-binding EGF-like growth factor gene expression in human keratinocytes and skin



Experimental Dermatology 7(6): 391-397



Retinoic acid (RA) has profound effects on epidermal homeostasis; however, the molecular mechanisms by which retinoids regulate keratinocyte cell proliferation and differentiation are not well understood. Here we report that mRNA expression of heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family of growth factors, is induced by RA in human keratinocytes and skin, and is overexpressed in the context of epidermal hyperplasia in vivo. Treatment of normal adult human keratinocytes with micromolar concentrations of RA significantly induced the expression of HB-EGF. The response was efficiently blocked by specific inhibitors of ErbB tyrosine kinase activity, MAP kinase kinase (MEK), or p38 stress-activated protein kinase. RA also enhanced the induction of HB-EGF mRNA in human skin organ culture, an ex vivo model system displaying many similarities to wound healing in vivo. HB-EGF transcripts were markedly increased in human skin by topical treatment with RA under conditions known to provoke epidermal hyperplasia. HB-EGF transcripts were also markedly overexpressed in the hyperplastic epidermis of psoriatic lesions, relative to normal skin. These results support the hypothesis that the effects of RA on epidermal hyperplasia are mediated at least in part by HB-EGF, and suggest that signal transduction mechanisms other than or in addition to nuclear RA receptors contribute to this effect.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 047261659

Download citation: RISBibTeXText

PMID: 9858142

DOI: 10.1111/j.1600-0625.1998.tb00339.x


Related references

Differential regulation of albumin gene expression by heparin-binding epidermal growth factor-like growth factor in alpha-fetoprotein-producing and -nonproducing human hepatoma cells. Tumour Biology 20(3): 130-138, 1999

Expression and regulation of messenger rna coding for heparin binding growth factors and transforming growth factor type alpha in human skin derived cells. Journal of Cell Biology 107(6 Part 3): 480A, 1988

Effects of acitretin and narrow-band UVB on the mRNA expression of heparin-binding epidermal growth factor like growth factor in normal human keratinocytes. 2007

Synergistic effects of acitretin and narrow-band UVB on inducing the expression of heparin-binding epidermal-growth-factor-like growth factor in normal human keratinocytes. Archives of Dermatological Research 299(8): 409-413, 2007

Regulation of amphiregulin a heparin binding egf like growth factor in human skin. Journal of Investigative Dermatology 98(4): 575, 1992

Regulation of heparin binding-epidermal growth factor like growth factor gene expression by LDL and oxidized-LDL in rat mesangial cells. Biochemical and Biophysical Research Communications 202(2): 1001-1008, 1994

Synergy between Rambazole (R115866) and retinoic acid alters the gene expression of heparin-binding EGF-like growth factor and involucrin in autocrine cultures of keratinocytes. 2007

Proteolysis of insulin-like growth factor-binding protein-3 by human skin keratinocytes in culture in comparison to that in skin interstitial fluid: the role and regulation of components of the plasmin system. Journal of Clinical Endocrinology and Metabolism 82(6): 1863-1868, 1997

Progesterone regulation of heparin-binding epidermal growth factor-like growth factor gene expression during sensitization and decidualization in the rat uterus: effects of the antiprogestin, ZK 98.299. Endocrinology 135(3): 1256-1263, 1994

Differential expression of heparin-binding EGF-like growth factor (HB-EGF) mRNA in normal human keratinocytes induced by a variety of natural and synthetic retinoids. Experimental Dermatology 12(Suppl. 2): 28-34, 2003

Expression of cytosolic retinoid-binding protein genes in human skin biopsies and cultured keratinocytes and fibroblasts. British Journal Of Dermatology. 131(2): 243-249, 1994

Temporal and spatial regulation of expression of heparin-binding epidermal growth factor-like growth factor in the human endometrium: a possible role in blastocyst implantation. Developmental Genetics 21(1): 102-108, 1997

Up-regulation of heparin binding epidermal growth factor-like growth factor and amphiregulin expression in Helicobacter pylori-infected human gastric mucosa. Digestive & Liver Disease 34(7): 498-505, 2002

Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin binding-EGF and amphiregulin in human skin in vivo. Journal of Investigative Dermatology 122(3): A49, 2004