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Insulin‐like growth factor binding protein‐3 (IGFBP‐3) localizes to and modulates proliferative epidermal keratinocytes in vivo
Author(s) -
Edmondson S.R.,
Thumiger S.P.,
Kaur P.,
Loh B.,
Koelmeyer R.,
Li A.,
Silha J.V.,
Murphy L.J.,
Wraight C.J.,
Werther G.A.
Publication year - 2005
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2004.06350.x
Subject(s) - keratinocyte , epidermis (zoology) , biology , keratinocyte growth factor , growth factor , epidermal growth factor , in situ hybridization , microbiology and biotechnology , insulin like growth factor binding protein , messenger rna , insulin like growth factor , receptor , in vitro , biochemistry , anatomy , gene
Summary Background The colocalization of insulin‐like growth factor binding protein‐3 (IGFBP‐3) and IGF‐I receptor (IGF‐IR) in the basal/germinative layer of the epidermis suggests a key role in modulating epidermal homeostasis. Objectives We aimed to clarify both the specific cellular localization and the effect of excess epidermal IGFBP‐3 on keratinocyte proliferation. Methods (i) Total RNA was isolated from fluorescence‐activated cell sorted basal human keratinocyte subtypes [keratinocyte stem cells, transit amplifying keratinocytes (TA), postmitotic differentiating keratinocytes (PMD)], and real‐time polymerase chain reaction analysis was used to determine the abundance of IGFBP‐3 and IGF‐IR mRNAs. (ii) An IGFBP‐3 transgenic mouse model was then used to assess the effect of excess epidermal IGFBP‐3 on keratinocyte proliferation. Excess epidermal IGFBP‐3 mRNA and protein was determined by in situ hybridization and immunohistochemistry, respectively. Results (i) The highest levels of IGFBP‐3 mRNA were detected in TA keratinocytes, in contrast to IGF‐IR mRNA levels which were highest in PMD keratinocytes. (ii) Elevated human IGFBP‐3 mRNA and protein was confirmed in the epidermis of skin derived from transgenic mice. Excess IGFBP‐3 reduced the relative percentage of proliferative keratinocytes (Ki67 positive) irrespective of skin location (belly, back and tail). Thus, in the epidermis, IGFBP‐3 mRNA is highly expressed by proliferative keratinocytes (TA) and overexpression of IGFBP‐3 inhibits keratinocyte proliferation. Conclusions We conclude that in vivo IGFBP‐3 ensures epidermal homeostasis via downregulation of keratinocyte proliferation, and thus modulates the early stages of keratinocyte differentiation.