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Mutual induction of growth factor gene expression by epidermal-dermal cell interaction
H Smola1, G Thiekötter, N E Fusenig
1Division of Differentiation and Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg.
The Journal of Cell Biology
|July 1, 1993
Summary
Epithelial-mesenchymal interactions, involving dermal cells and keratinocytes, control skin growth and repair. This study reveals paracrine factors and cell-cell contact are crucial for epidermal homeostasis.
Area of Science:
- Dermal biology
- Skin biology
- Cell biology
Background:
- Epithelial-mesenchymal interactions regulate epidermal growth and differentiation.
- Mechanisms underlying these interactions remain largely unknown.
Purpose of the Study:
- To investigate the effects of human dermal microvascular endothelial cells (DMEC) and fibroblasts on keratinocytes.
- To elucidate the role of paracrine factors and cell-cell interactions in epidermal homeostasis.
Main Methods:
- Conventional (feeder layer) and organotypic cocultures (lifted collagen gels) were used.
- Keratinocyte and dermal cell proliferation and gene expression (KGF, IL-6, GM-CSF) were analyzed.
- Differentiation markers and keratin localization were assessed.
- In vivo studies involved surface transplants on nude mice.
Main Results:
- Coculture with DMEC and fibroblasts stimulated keratinocyte proliferation via induced paracrine growth factor gene expression.
- Keratinocytes stimulated mRNA levels for KGF and IL-6 in dermal cells, and GM-CSF in fibroblasts.
- Organotypic cocultures formed a near-normal epidermis with stimulated keratinocyte proliferation.
- Differentiation markers showed altered localization, resembling epidermal hyperplasia, but normalized in vivo.
Conclusions:
- Epidermal homeostasis is regulated by reciprocal paracrine factors, cell-cell interactions, and extracellular matrix influences.
- Complex epithelial-mesenchymal crosstalk is essential for maintaining skin structure and function.