Article

Immunohistochemical localization of basic fibroblast growth factor in wound healing sites of mouse skin.

Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan.
Archives for Dermatological Research (impact factor: 2.28). 02/1992; 284(4):193-7. pp.193-7
Source: PubMed

ABSTRACT The immunohistochemical localization of basic fibroblast growth factor (bFGF) was examined during wound healing in mouse skin. Frozen sections taken from the rounded skin defects were reacted with polyclonal anti-human recombinant bFGF IgG followed by incubation with FITC-conjugated IgG. The basal layer keratinocytes and hair bulbs at the wound edge were strongly stained with this antibody. In the reepithelized area, several layers of keratinocytes from the basal layer were positively stained regardless of the time after wounding. These findings suggest that germinative keratinocytes which express bFGF function as leading cells in the covering of the wound defect. However, dermal granulation tissue, including capillary endothelial cells, fibroblasts and macrophages unexpectedly did not demonstrate any immunoreactivity throughout the process of wound healing. Simultaneous histochemical investigation using cultivated mouse keratinocytes and bovine aortic endothelial cells showed primarily cytoplasmic fluorescence. The discrepancy in the staining patterns of endothelial cells in vivo and in vitro suggests that immunoreactive bFGF is either not expressed in vivo, or is processed or masked.

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    Article: Loss of vascular endothelial growth factor a activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation.
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    ABSTRACT: The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a central role in both wound healing and tumor growth. In the skin, epidermal keratinocytes are a major source of this growth factor. To study the contribution of keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we generated mice in which this cytokine was inactivated specifically in keratin 5-expressing tissues. The mutant mice were macroscopically normal, and the skin capillary system was well established, demonstrating that keratinocyte-derived VEGF-A is not essential for angiogenesis in the skin during embryonic development. However, healing of full-thickness wounds in adult animals was appreciably delayed compared with controls, with retarded crust shedding and the appearance of a blood vessel-free zone underneath the newly formed epidermis. When 9,12-dimethyl 1,2-benzanthracene was applied as both tumor initiator and promoter, a total of 143 papillomas developed in 20 of 23 (87%) of control mice. In contrast, only three papillomas arose in 2 of 17 (12%) of the mutant mice, whereas the rest merely displayed epidermal thickening and parakeratosis. Mutant mice also developed only 2 squamous cell carcinomas, whereas 11 carcinomas were found in seven of the control animals. These data demonstrate that whereas keratinocyte-derived VEGF-A is dispensable for skin vascularization under physiological conditions, it plays an important albeit nonessential role during epidermal wound healing and is crucial for the development of 9,12-dimethyl 1,2-benzanthracene-induced epithelial skin tumors.
    Cancer Research 06/2004; 64(10):3508-16. · 7.86 Impact Factor

Keywords

basal layer
 
basal layer keratinocytes
 
bovine aortic endothelial cells
 
capillary endothelial cells
 
cytoplasmic fluorescence
 
dermal granulation tissue
 
endothelial cells
 
express bFGF function
 
FITC-conjugated IgG
 
Frozen sections
 
germinative keratinocytes
 
mouse keratinocytes
 
mouse skin
 
polyclonal anti-human recombinant bFGF IgG
 
reepithelized area
 
rounded skin defects
 
Simultaneous histochemical investigation
 
staining patterns
 
wound edge
 
wound healing
 

Y Kurita