Biphasic regulation of AP-1 subunits during human epidermal wound healing.
Cutaneous wound healing is a well-coordinated process that includes inflammation, proliferation, and differentiation. Activator protein 1 (AP-1) subunits have been implicated in the regulation of genes important for these processes and have been shown to be involved in wound healing. However, investigation of human healing and non-healing wounds in vivo and ex vivo, and the comparative analysis of several members of the Jun and Fos families are still missing. Here, we show that normal human epidermal wound healing is biphasic. In the first phase all AP-1 subunits investigated, that is c-Jun, Jun B, Jun D, c-Fos, and Fos B are absent from the nuclei at the wound margins/leading edges. This downregulation coincides with that of the gap junction protein connexin 43. Later on, c-Jun, Jun B, Jun D, and c-Fos reappear in the nuclei of the leading edges in a time-dependent manner. In non-healing wounds, a more intensive staining of keratinocytes at the wound margins is often observed. Our findings suggest that coordinated down- and upregulation of the various AP-1 subunits in the course of epidermal wound healing is important for its undisturbed progress, putatively by influencing inflammation and cell-cell communication.
Neub
Angela
A
Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Houdek
Pia
P
Ohnemus
Ulrich
U
Moll
Ingrid
I
Brandner
Johanna M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D018031:Connexin 43 / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
D018031:Connexin 43; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1