Epidermal signal transduction and transcription factor activation in activated keratinocytes

Marjana Tomic-Canic, Mayumi Komine, Irwin M. Freedberg, Miroslav Blumenberg

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

In the area of biology, many laboratories around the world are dissecting and characterizing signal transduction mechanisms and transcription factors responsive to various growth factors and cytokines, in various cell types. However, because of the differences in systems used, it is not clear whether these systems coexist, whether they interact meaningfully, and what their relative roles are. Epidermal keratinocytes are the perfect cell type in which to integrate this knowledge, because in these cells these mechanisms are known to be relevant. Keratinocytes both produce and respond to growth factors and cytokines, especially in pathological conditions and during wound healing, when the physiology of keratinocytes is altered in a way specified by the presence of a subset growth factors and cytokines. In fact, growth factors and cytokines cause the major changes in gene expression and keratinocyte behavior in various cutaneous diseases. In some cases, such as in wound healing, these responses are highly beneficial; in others, such as in psoriasis, they are pathological. It is not clear at present which are operating in which conditions, which are important for the healing process and which are harmful. Growth factors and cytokines affect keratinocytes sometimes simultaneously, at other times individually. In this manuscript we describe the signal transduction pathways responsible for the effects of interferons, the EGF/TGFα family and the TNFα/IL-1 family of signaling molecules. We also describe the important transcription factors known to be functional in epidermis, with particular emphasis on those factors that are activated by growth factors and cytokines. Finally, we describe what is known about transcriptional regulation of keratin genes, especially those specifically expressed in pathological processes in the epidermis. We expect that the enhanced understanding of the pathways regulating gene expression in keratinocytes will identify the pharmacological targets, the signal transducing proteins and the corresponding transcription factors, used by growth factors and cytokines. This research will lead to development of compounds precisely aimed at those targets, allowing us to isolate and inhibit the harmful side effects of growth factors and cytokines. Such compounds should lead to highly specific and therefore more effective treatments of the cutaneous disorders in which these pathways play significant roles.

Original languageEnglish
Pages (from-to)167-181
Number of pages15
JournalJournal of Dermatological Science
Volume17
Issue number3
DOIs
StatePublished - Jul 1 1998
Externally publishedYes

Fingerprint

Signal transduction
Keratinocytes
Transcriptional Activation
Signal Transduction
Intercellular Signaling Peptides and Proteins
Transcription Factors
Chemical activation
Cytokines
Gene expression
Epidermis
Wound Healing
Lead compounds
Gene Expression
Physiology
Pathologic Processes
Keratins
Interleukin-1
Psoriasis
Skin Diseases
Epidermal Growth Factor

Keywords

  • Epidermal signal transduction
  • Keratinocyte
  • Transcription factor activation

ASJC Scopus subject areas

  • Dermatology

Cite this

Epidermal signal transduction and transcription factor activation in activated keratinocytes. / Tomic-Canic, Marjana; Komine, Mayumi; Freedberg, Irwin M.; Blumenberg, Miroslav.

In: Journal of Dermatological Science, Vol. 17, No. 3, 01.07.1998, p. 167-181.

Research output: Contribution to journalArticle

Tomic-Canic, Marjana ; Komine, Mayumi ; Freedberg, Irwin M. ; Blumenberg, Miroslav. / Epidermal signal transduction and transcription factor activation in activated keratinocytes. In: Journal of Dermatological Science. 1998 ; Vol. 17, No. 3. pp. 167-181.
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