PMID- 10199559
OWN - NLM
STAT- MEDLINE
DCOM- 19990427
LR  - 20061115
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 179
IP  - 2
DP  - 1999 May
TI  - Expression of insulin-like growth factor binding protein-3 (IGFBP-3) in human 
      keratinocytes is regulated by EGF and TGFbeta1.
PG  - 201-7
AB  - Insulin-like growth factor-I (IGF-I) is essential for normal epidermal 
      homeostasis; however, the role of IGF binding proteins (IGFBPs), regulators of 
      IGF action, remains unclear. Here we examine the regulation of human 
      keratinocyte-produced IGFBPs by epidermal growth factor (EGF), transforming 
      growth factor beta 1 (TGFbeta1), and IGF-I, growth factors known to be active in 
      skin. In the absence of added growth factors, IGFBP-3 was the major binding 
      protein secreted into the medium by primary keratinocytes. Addition of EGF or 
      TGFbeta1 to keratinocyte cultures resulted in a significant decrease in IGFBP-3 
      abundance in conditioned medium when compared with control, untreated cells. 
      Specifically, EGF (50 ng/ml) and TGFbeta1 (50 ng/ml) reduced IGFBP-3 abundance to 
      15+/-6% and 22+/-9%, respectively. Using Northern blot analysis, we found EGF and 
      TGFbeta1 (50 ng/ml) to reduce IGFBP-3 mRNA levels in keratinocytes to 51+/-12% 
      and 50+/-38%, respectively, when compared with control, untreated cells. 
      Treatment with IGF-I or its analogue des(1-3)IGF-I did not lead to any consistent 
      change in IGFBP-3 abundance. However, both IGF-I and des(1-3)IGF-I at 100 ng/ml 
      led to a modest increase in IGFBP-3 mRNA levels in keratinocytes, suggesting 
      posttranscriptional regulation of IGFBP-3 abundance. We propose that local 
      modulation of IGFBP-3 abundance may represent another level of regulation of 
      growth factor action in the epidermis, where EGF and TGFbeta1 and possibly other 
      local growth factors specifically regulate the availability of IGF-I to its 
      keratinocyte receptors.
FAU - Edmondson, S R
AU  - Edmondson SR
AD  - Centre for Hormone Research, Royal Children's Hospital, Parkville, Victoria, 
      Australia.
FAU - Murashita, M M
AU  - Murashita MM
FAU - Russo, V C
AU  - Russo VC
FAU - Wraight, C J
AU  - Wraight CJ
FAU - Werther, G A
AU  - Werther GA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 112603-35-7 (insulin-like growth factor 1, des-(1-3)-)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Culture Media, Conditioned/pharmacology
MH  - Epidermal Growth Factor/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/*genetics/metabolism
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Keratinocytes/drug effects/*metabolism
MH  - Peptide Fragments/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Skin/drug effects
MH  - Transforming Growth Factor beta/*pharmacology
EDAT- 1999/04/13 02:08
MHDA- 2000/06/20 09:00
CRDT- 1999/04/13 02:08
PHST- 1999/04/13 02:08 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/04/13 02:08 [entrez]
AID - 10.1002/(SICI)1097-4652(199905)179:2<201::AID-JCP10>3.0.CO;2-9 [pii]
AID - 10.1002/(SICI)1097-4652(199905)179:2<201::AID-JCP10>3.0.CO;2-9 [doi]
PST - ppublish
SO  - J Cell Physiol. 1999 May;179(2):201-7. doi: 
      10.1002/(SICI)1097-4652(199905)179:2<201::AID-JCP10>3.0.CO;2-9.