HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Autocrine regulation of keratinocytes: the emerging role of heparin-binding, epidermal growth factor-related growth factors.

Abstract
Although originally conceived as a basis for malignant cell growth, autocrine signaling networks are currently known to be activated during tissue repair and with in vitro cultivation. In human epidermal keratinocytes, activation of the epidermal growth factor receptor by cognate ligands mediates the majority of the autonomous replicative capacity of these cells and is necessary to inhibit differentiation and apoptosis. The importance of heparin-binding growth factors in activation of this receptor was first suggested by the strong anti-proliferative effects of soluble heparin-like molecules on keratinocyte growth. This and related evidence led to the identification of amphiregulin as a major autocrine factor for keratinocytes. The binding of amphiregulin and its homolog, heparin-binding epidermal growth factor-like growth factor, to the receptor is potentially amplified by autoinduction and cross-signaling through epidermal growth factor-related polypeptides and by transmodulation of other ErbB-family receptors (HER-2, -3, -4) in cells expressing these receptors. Heparan sulfate proteoglycans and the tetraspanin family of membrane-associated proteins appear to act as cofactors in amphiregulin-driven mitogenesis mediated by the epidermal growth factor receptor, but amphiregulin's immunolocalization to keratinocyte nuclei and to filopodia may indicate other potentially novel effects. Following from the observation that amphiregulin is overexpressed in lesional psoriatic epidermis, the importance of amphiregulin in hyperproliferative skin diseases has been further supported by recent studies of the targeted expression of a transgene encoding keratin 14 promoter-driven human amphiregulin to the basal epidermis of mice. Founder transgenic mice displayed a morphologic and microscopic cutaneous phenotype that shares characteristics with psoriasis. Pharmacologic regulation of amphiregulin's expression and receptor signaling may eventually prove to be an effective strategy in the treatment of hyperproliferative skin diseases.
AuthorsM Piepkorn, M R Pittelkow, P W Cook
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 111 Issue 5 Pg. 715-21 (Nov 1998) ISSN: 0022-202X [Print] United States
PMID9804327 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References
  • AREG protein, human
  • Amphiregulin
  • Areg protein, mouse
  • EGF Family of Proteins
  • Glycoproteins
  • Growth Substances
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Epidermal Growth Factor
  • Heparin
Topics
  • Amphiregulin
  • Animals
  • Cell Transformation, Neoplastic (drug effects)
  • EGF Family of Proteins
  • Epidermal Growth Factor (physiology)
  • Glycoproteins (genetics)
  • Growth Substances (genetics)
  • Heparin (physiology)
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Keratinocytes (cytology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: