NF1 tumor suppressor in epidermal wound healing with special focus on wound healing in patients with type 1 neurofibromatosis.
Type 1 neurofibromatosis syndrome (NF1) has been linked with mutations of the NF1 gene which encodes tumor suppressor neurofibromin, a regulator of Ras-MAPK signaling. In human epidermis, keratinocytes express NF1 tumor suppressor and it may have a distinctive function in these cells during wound healing, such as regulating Ras activity. NF1 expression was first studied during the epidermal wound healing using suction blister method. NF1 gene expression increased both in hypertrophic and migrating zones of the healing epidermis, and also in dermal fibroblasts underneath the injury. This prompted us to study epidermal wound healing in NF1 patients. Wound healing efficiency was evaluated 4 days after blister induction by clinical, physiological and histological methods. Epidermal wound healing was equally effective in NF1 patients and healthy controls. In addition, dermal wound healing appears to function normally in NF1 patients based on retrospective and follow-up study of biopsy scars. Furthermore, the healing wounds were analyzed immunohistochemically for cell proliferation rate and Ras-MAPK activity. Neither epidermal keratinocytes nor dermal fibroblasts showed difference in the cell proliferation rate or Ras-MAPK activity between NF1 patients and controls. Interestingly, NF1 patients displayed increased cell proliferation rate and Ras-MAPK activity in periarteriolar tissue underneath the wound. The results of the study suggest that epidermal wound healing is not markedly altered in NF1 patients. Furthermore, NF1 protein seems not to have an important function as a Ras-MAPK regulator in epidermal keratinocytes or dermal fibroblasts but instead appears to be regulator of Ras-MAPK signaling in vascular tissues.
Koivunen
Jussi
J
Department of Anatomy and Cell Biology, University of Oulu, Oulu, PB 5000, 90014, Finland. jkoivune@raita.oulu.fi
Karvonen
Seija-Liisa
SL
Ylä-Outinen
Heli
H
Aaltonen
Vesa
V
Oikarinen
Aarne
A
Peltonen
Juha
J
D049109:Cell Proliferation; D004548:Elasticity; D016514:Genes, Neurofibromatosis 1 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009456:Neurofibromatosis 1 / Q000503:physiopathology*; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply / Q000293:injuries*; D014945:Wound Healing
D019394:Ki-67 Antigen; D020928:Mitogen-Activated Protein Kinases