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

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

S W Stoll et al. Exp Dermatol. 1998 Dec.

Free article

Abstract

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.

Similar articles

• Heparin-binding epidermal-growth-factor-like growth factor activation of keratinocyte ErbB receptors Mediates epidermal hyperplasia, a prominent side-effect of retinoid therapy.

  Varani J, Zeigler M, Dame MK, Kang S, Fisher GJ, Voorhees JJ, Stoll SW, Elder JT. Varani J, et al. J Invest Dermatol. 2001 Dec;117(6):1335-41. doi: 10.1046/j.0022-202x.2001.01564.x. J Invest Dermatol. 2001. PMID: 11886492

• 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.

  Yoshimura K, Uchida G, Okazaki M, Kitano Y, Harii K. Yoshimura K, et al. Exp Dermatol. 2003;12 Suppl 2:28-34. doi: 10.1034/j.1600-0625.12.s2.5.x. Exp Dermatol. 2003. PMID: 14756521

• The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes.

  Giltaire S, Herphelin F, Frankart A, Hérin M, Stoppie P, Poumay Y. Giltaire S, et al. Br J Dermatol. 2009 Mar;160(3):505-13. doi: 10.1111/j.1365-2133.2008.08960.x. Epub 2008 Dec 11. Br J Dermatol. 2009. PMID: 19120344

• ErbB and HB-EGF signaling in heart development and function.

  Iwamoto R, Mekada E. Iwamoto R, et al. Cell Struct Funct. 2006;31(1):1-14. doi: 10.1247/csf.31.1. Cell Struct Funct. 2006. PMID: 16508205 Review.

• Members of the EGF receptor family in normal and pathological epidermis.

  Poumay Y, Mitev V. Poumay Y, et al. Folia Med (Plovdiv). 2009 Jul-Sep;51(3):5-17. Folia Med (Plovdiv). 2009. PMID: 19957557 Review.

Cited by

• Epidermal Hyperplasia and Elevated HB-EGF are More Prominent in Retinoid Dermatitis Compared with Irritant Contact Dermatitis Induced by Benzalkonium Chloride.

  Lee JE, Chang JY, Lee SE, Kim MY, Lee JS, Lee MG, Kim SC. Lee JE, et al. Ann Dermatol. 2010 Aug;22(3):290-9. doi: 10.5021/ad.2010.22.3.290. Epub 2010 Aug 5. Ann Dermatol. 2010. PMID: 20711265 Free PMC article.

• Preclinical assessment of dual CYP26[A1/B1] inhibitor, DX308, as an improved treatment for keratinization disorders.

  Veit JGS, Poumay Y, Mendes D, Kreitinger J, Walker L, Paquet A, Menigot C, Zolezzi F, Paller AS, Diaz P. Veit JGS, et al. Skin Health Dis. 2021 Mar 26;1(2):e22. doi: 10.1002/ski2.22. eCollection 2021 Jun. Skin Health Dis. 2021. PMID: 35664983 Free PMC article.

• Autocrine extracellular signal-regulated kinase (ERK) activation in normal human keratinocytes: metalloproteinase-mediated release of amphiregulin triggers signaling from ErbB1 to ERK.

  Kansra S, Stoll SW, Johnson JL, Elder JT. Kansra S, et al. Mol Biol Cell. 2004 Sep;15(9):4299-309. doi: 10.1091/mbc.e04-03-0233. Epub 2004 Jul 14. Mol Biol Cell. 2004. PMID: 15254267 Free PMC article.

• Characterization of CYP26B1-Selective Inhibitor, DX314, as a Potential Therapeutic for Keratinization Disorders.

  Veit JGS, De Glas V, Balau B, Liu H, Bourlond F, Paller AS, Poumay Y, Diaz P. Veit JGS, et al. J Invest Dermatol. 2021 Jan;141(1):72-83.e6. doi: 10.1016/j.jid.2020.05.090. Epub 2020 Jun 4. J Invest Dermatol. 2021. PMID: 32505549 Free PMC article. Review.

• Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid.

  Ahrens JM, Jones JD, Nieves NJ, Mitzey AM, DeLuca HF, Clagett-Dame M. Ahrens JM, et al. PLoS One. 2017 Nov 28;12(11):e0188887. doi: 10.1371/journal.pone.0188887. eCollection 2017. PLoS One. 2017. PMID: 29182680 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • MLibrary (Deep Blue)
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal