Insutin-like growth factor binding protein-3 (IMP-3) tocatizes to and modutates protiferative epidermat keratinocytes in vivo

被引:36
作者
Edmondson, SR
Thumiger, SP
Kaur, P
Loh, B
Koelmeyer, R
Li, A
Silha, JV
Murphy, LJ
Wraight, CJ
Werther, GA
机构
[1] Royal Childrens Hosp, Murdoch Childrens Res Inst, Ctr Hormone Res, Cutaneous Biol Grp, Parkville, Vic 3052, Australia
[2] Univ Melbourne, Parkville, Vic 3052, Australia
[3] Peter MacCallum Canc Inst, Epithelial Stem Cell Biol Lab, Melbourne, Vic 3002, Australia
[4] Univ Manitoba, Dept Physiol & Med, Winnipeg, MB R3E 3P4, Canada
关键词
epidermal homeostasis; IGF; IGFBP; keratinocyte;
D O I
10.1111/j.1365-2133.2004.06350.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 [皮肤病与性病学];
摘要
Background The colocalization of insulin-like growth factor binding protein-3 (XGFBP-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 realtime 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. (h) 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.
引用
收藏
页码:225 / 230
页数:6
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