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- Title
A Keratinocyte Cell Line Synthesizes a Predominant Insulin-Like Growth Factor-Binding Protein (IGFBP-3) that Modulates Insulin-Like Growth Factor-I Action.
- Authors
Wraight, Christopher J.; Murashita, Mari M.; Russo, Vincenzo C.; Werther, George A.
- Abstract
Insulin-like growth factor-I (IGF-I) is an important regulator of epidermal proliferation and has been shown <em>in vitro</em> to be a powerful stimulator of keratinocyte growth. It is synthesized by fibroblasts in the dermis, along with several IGF-binding proteins (IGFBPs), which are known to modulate IGF-I responsiveness of virtually all tissues studied. Because it was not known how or in what form IGF-I produced in the dermis acts on epidermal keratinocytes <em>in vivo</em>, we investigated the possible role of IGFBPs in modulating the response of epidermal keratinocytes to IGF-1. We show here that tIGF-I, a non -- IGFBP-binding analogue of IGE- 1, is a more potent mitogenic stimulator of the keratinocyte cell line HaCaT than IGF-I, suggesting that keratinocytes produce IGFBPs that modulate their response to IGF-I. To confirm this and to identify which IGFBPs were produced, we analyzed HaCaT cell -- conditioned medium and mRNA, with the following findings: HaCaT cells produce a major IGFBP, identified as IGFBP-3, and a minor 24-kD IGFBP, likely to be IGFBP-4. Northern analysis revealed a 2.6-kb IGFBP-3 mRNA; however, IGFBP-4 mRNA was not detectable. We conclude that production of predominantly IGFBP-3 by the HaCaT cell line modulates its sensitivity to IGF-I stimulation. Epidermal IGFBPs thus have a potential role <em>in vivo</em> in the interaction of dermis derived IGF-I with epidermal keratinocytes.
- Subjects
KERATINOCYTES; INSULIN; GROWTH factors; PROTEINS; EPIDERMIS; HORMONES
- Publication
Journal of Investigative Dermatology, 1994, Vol 103, Issue 5, p627
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12397667