Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha.
Transforming growth factor-alpha(TGF-alpha), homologous to epidermal growth factor(EGF), is closely involved in hyperproliferation of human keratinocytes. Psoriasis is a common hyperproliferative skin disease characterized by hyperproliferation of keratinocytes and abnormal development of dermal capillary networks. In this study, we have examined whether keratinocytes could enhance angiogenesis. TGF-alpha or EGF efficiently stimulated formation of tubular-like structures of human omental microvascular endothelial(HOME) cells in type I collagen gels. Human keratinocytes produced TGF-alpha. To examine whether co-cultured keratinocytes could induce tubulogenesis of HOME cells in collagen gel, we have developed a co-culture system with human keratinocytes. Surprisingly, there appeared new development of many tubular-like structures of HOME cells in collagen gels when co-cultured with keratinocytes. This keratinocytes-dependent tubulogenesis was almost completely blocked when anti-TGF-alpha-antibody was present. The TGF-alpha molecules derived from keratinocytes appeared to enhance tubulogenesis of human microvascular endothelial cells. We propose the hypothesis that secretory TGF-alpha from human keratinocytes may promote an autocrine loop to proliferate the skin keratinocytes and also a paracrine loop to induce the skin angiogenesis.
D015152:Blotting, Northern; D002450:Cell Communication; D002478:Cells, Cultured; D015342:DNA Probes; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008833:Microcirculation; D009852:Omentum / Q000098:blood supply; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
D015342:DNA Probes; D010710:Phosphates; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D012313:RNA; D066246:ErbB Receptors