TY - JOUR
T1 - The Insulin-like Growth Factor 1 Receptor Is Expressed by Epithelial Cells with Proliferative Potential in Human Epidermis and Skin Appendages
T2 - Correlation of Increased Expression with Epidermal Hyperplasia
AU - Hodak, Emmilia
AU - Gottlieb, Alice B.
AU - Anzilotti, Michele
AU - Krueger, James G.
PY - 1996
Y1 - 1996
N2 - Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitro, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo. In this study, we used a monoclonal antibody (α-IR3) that binds to the α-chain of this receptor to study its expression (i) in other epithelial cell types in human skin and (ii) in growth-activated epidermis associated with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-like or undifferentiated germinative epithelial cells associated with the follicular outer root sheath, sebaceous glands, and the hair matrix. There was minimal IGF-1 receptor expression hi differentiating outer root sheath, hair shaft, and sebaceous epithelial cells. IGF-1 receptor expression in non-growth-activated epidermis of long-standing seborrheic keratoses was confined to the basal epidermal layer, as in normal epidermis. In contrast, hyperplastic epidermis undergoing "regenerative" differentiation (keratin 16+, Ki67+ suprabasal keratinocytes) from psoriasis, chronic skin wounds, and plaques of mycosis fungoides consistently showed increased expression of IGF-1 receptor. In these conditions, the region of expanded IGF-1 receptor expression delimited the epidermal zone of keratinocyte proliferation. In cultured keratinocytes, the subcellular localization of the IGF-1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding, suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation. Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that receptor expression can be modulated with differing epidermal growth states, and that these receptors are largely downregulated in highly differentiated epithelial cells.
AB - Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitro, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo. In this study, we used a monoclonal antibody (α-IR3) that binds to the α-chain of this receptor to study its expression (i) in other epithelial cell types in human skin and (ii) in growth-activated epidermis associated with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-like or undifferentiated germinative epithelial cells associated with the follicular outer root sheath, sebaceous glands, and the hair matrix. There was minimal IGF-1 receptor expression hi differentiating outer root sheath, hair shaft, and sebaceous epithelial cells. IGF-1 receptor expression in non-growth-activated epidermis of long-standing seborrheic keratoses was confined to the basal epidermal layer, as in normal epidermis. In contrast, hyperplastic epidermis undergoing "regenerative" differentiation (keratin 16+, Ki67+ suprabasal keratinocytes) from psoriasis, chronic skin wounds, and plaques of mycosis fungoides consistently showed increased expression of IGF-1 receptor. In these conditions, the region of expanded IGF-1 receptor expression delimited the epidermal zone of keratinocyte proliferation. In cultured keratinocytes, the subcellular localization of the IGF-1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding, suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation. Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that receptor expression can be modulated with differing epidermal growth states, and that these receptors are largely downregulated in highly differentiated epithelial cells.
KW - Keratinocyte
KW - Regenerative epidermal growth
UR - http://www.scopus.com/inward/record.url?scp=0029932093&partnerID=8YFLogxK
U2 - 10.1111/1523-1747.ep12344044
DO - 10.1111/1523-1747.ep12344044
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C2 - 8648195
AN - SCOPUS:0029932093
SN - 0022-202X
VL - 106
SP - 564
EP - 570
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -