Recent studies have shown that adult skin incubated in low- @entity141 (0.15 mM) medium rapidly degenerates but that normal architecture is maintained when the tissue is incubated in high- @entity141 medium (1.4 mM @entity141 ). To investigate whether the skin cell-produced growth factors @entity442 ( @entity442 ) and epidermal growth factor (EGF) play a role in these events, 2-mm skin punch biopsies were obtained and maintained for 8 to 10 days in a basal medium containing 0.15 mM @entity141 with and without growth factors, or containing 1.4 mM @entity141 with and without antibodies to the same growth factors. In parallel experiments, cultured @entity1 keratinocytes were incubated for 2 days in the same basal medium in the presence or absence of the same growth factors and antibodies. Consistent with previous reports, organ cultures incubated in the low- @entity141 (0.15 mM) medium rapidly degenerated. Neither @entity442 nor EGF prevented the complete degeneration of epidermis and dermis in these organ cultures. Interestingly, the addition of an @entity2856 ( @entity2856 ) antibody to the organ cultures maintained in high- @entity141 medium induced changes reminiscent of those seen when the organ cultures were maintained in low- @entity141 medium, i.e. @entity528 . In contrast, antibodies to EGF receptor, used for comparison, only produced focal areas of epidermal @entity39 . In vitro, @entity442 is a known mitogen for keratinocytes. In cultured human keratinocytes, anti- @entity2856 antibody partially inhibited the @entity442 -mediated stimulation of @entity1 keratinocyte proliferation without affecting normal spontaneous growth. Additionally, @entity2856 immunolocalized to basal keratinocytes in vivo, exhibited specific binding to @entity442 in vitro. This indicated a critical role for @entity2856 in both organ cultures ex vivo and cultured cells in vitro. Messenger RNA encoding both @entity442 and @entity2856 were readily detected by RT-PCR in organ cultures incubated in both low- and high- @entity141 medium. There were no detectable differences in @entity442 mRNA in organ cultures growing in the low- or high- @entity141 medium, but lower levels of @entity2856 mRNA were observed in the organ cultures maintained in low- @entity141 medium than in those in high @entity141 medium. These findings are consistent with homeostatic changes in the tissue grown under different @entity460 concentrations. @entity442 mRNA was detected in several skin cell populations in vitro, even though it was undetectable in cultured keratinocytes. Taken together these findings indicate that (1) the @entity442 / @entity2856 loop is critically involved in maintenance of @entity1 skin organ cultures ex vivo, and (2) @entity442 , locally produced by skin cells other than keratinocytes, interacts with its receptor, predominantly expressed in basal keratinocytes, to maintain tissue homeostasis.

Maintenance of XXXX skin in organ culture: role for @entity2856 and epidermal growth factor receptor.

@entity1 :: ('9606', 'Species') :: ['human'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity442 :: ('3479', 'Gene') :: ['insulin-like growth factor-1', 'IGF-1'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity2856 :: ('3480', 'Gene') :: ['IGF-1R', 'anti-IGF-1 receptor'] @entity528 :: ('MESH:D009410', 'Disease') :: ['tissue degeneration']
@entity1 :: (9606,Species) :: ['human']
