UV induced responses of the human epidermal IGF system: impaired anti-apoptotic effects of IGF-I in HaCaT keratinocytes.
The insulin-like growth factor receptor (IGF-IR) is critical in epidermal development and IGF binding protein-3 (IGFBP-3), a modulator of cellular activity with or without IGF-dependence, co-localises with epidermal IGF-IRs. We have investigated whether the greater UV susceptibility of a human keratinocyte cell line (HaCaT) in comparison to normal human keratinocytes (NHKs) may involve differences in the IGF system. At 24 h after UV (960 mJ/cm(2) UVB), in comparison to NHKs, HaCaT keratinocytes exhibited significantly higher levels of apoptosis, refractoriness to IGF-I treatment and reduced IGF-IR phosphorylation. Secreted, intact IGFBP-3 (38-42 kDa) and IGFBP-3 mRNA abundance were reduced in HaCaT keratinocytes, but not consistently altered in NHKs. Immunoreactive IGFBP-3 fragments (16-11 kDa) were detected in both UV-exposed cultures. These data suggest that an altered IGF system contributes to HaCaT keratinocyte UV susceptibility and that following UV insult the IGF system may enhance keratinocyte viability and contribute to a return to epidermal homeostasis.
Thumiger
Susan P
SP
Centre for Hormone Research, Murdoch Childrens Research Institute, Royal Children's Hospital, University of Melbourne, Flemington Road, Parkville, Victoria, Australia.
Adams
Timothy E
TE
Werther
George A
GA
Wraight
Christopher J
CJ
Edmondson
Stephanie R
SR
D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004817:Epidermis / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D008024:Ligands; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry; D014466:Ultraviolet Rays
D018972:Insulin-Like Growth Factor Binding Protein 3; D008024:Ligands; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I