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Wound reepithelialization activates a growth factor‐responsive enhancer in migrating keratinocytes
Author(s) -
Jaakkola Panu,
Kontusaari Sirpa,
Kauppi Tuire,
Määttä Arto,
Jalkanen Markku
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.11.959
Subject(s) - microbiology and biotechnology , wound healing , keratinocyte , signal transduction , biology , syndecan 1 , kinase , growth factor , extracellular matrix , keratinocyte growth factor , mapk/erk pathway , enhancer , transcription factor , receptor , cell , gene , immunology , cell culture , biochemistry , genetics
Wound reepithelialization and keratinocyte migration require strictly ordered gene expression, which is assumed to be initiated by locally released mitogens and exposure of the cells to different matrix components. The mechanisms triggering gene expression specifically during reepithelialization are poorly understood. The far upstream AP‐1‐driven, FGF‐inducible response element (FiRE) of the syndecan‐1 gene was activated during cutaneous wound healing in transgenic mice. FiRE was induced selectively in migrating but not in proliferating keratinocytes at the wound edge. The activation was initiated at the start of the cell migration, was persistent throughout the merging and stratification phases, and was terminated after completion of reepithelialization. Although FiRE has been found within the gene of syndecan‐1, the proximal promoter of syndecan‐1 was not required for activation of FiRE in the migrating keratinocytes. The wounding induced activation was inhibited by blocking cell surface growth factor receptors with suramin. However, the activation of FiRE in resting skin required simultaneous growth factor‐ and stress‐induced signals, but could also be elicited by the phosphatase inhibitor, okadaic acid. The activation by both wounding and chemical stimuli was blocked by inhibiting extracellular regulated kinase and p38 MAP kinases, suggesting the involvement of at least two parallel signal transduction pathways in wounding induced gene activation. As FiRE shows specificity for migrating keratinocytes only, it can be a useful tool for future wound healing studies and for targeting genes to injured tissues.—Jaakkola, P., Kontusaari, S., Kauppi, T., Määttä, A., Jalkanen, M. FASEB J. 12, 959–969 (1998)