J Cell Physiol 1999,
PMID: 10199559
Edmondson, S R; Murashita, M M; Russo, V C; Wraight, C J; Werther, G A
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.
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Text Mining Data
protein-3 → TGFbeta1: "
Expression of insulin-like growth factor binding
protein-3 ( IGFBP-3 ) in human keratinocytes is
regulated by EGF and
TGFbeta1
"
protein-3 → EGF: "
Expression of insulin-like growth factor binding protein-3 ( IGFBP-3 ) in human keratinocytes is regulated by EGF and TGFbeta1
"
insulin-like growth factor → TGFbeta1: "
Expression of insulin-like growth factor binding protein-3 ( IGFBP-3 ) in human keratinocytes is regulated by EGF and TGFbeta1
"
insulin-like growth factor → EGF: "
Expression of insulin-like growth factor binding protein-3 ( IGFBP-3 ) in human keratinocytes is regulated by EGF and TGFbeta1
"
IGFBP-3 ⊣ TGFbeta1: "
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
"
IGFBP-3 ⊣ EGF: "
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
"
IGFBP-3 → IGF-I: "
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
"
Manually curated Databases
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