Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro

Journal Article · Sat Jul 01 00:00:00 EDT 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.02.025· OSTI ID:20857990

Siemes, Christina ^[1]; Quast, Thomas ^[1]; Kummer, Christiane ^[1]; Wehner, Sven ^[1]; Kirfel, Gregor ^[1]; Mueller, Ulrike ^[2]; Herzog, Volker ^[1]

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1. Institute of Cell Biology and Bonner Forum Biomedizin, University of Bonn, Ulrich-Haberlandstr. 61A, 53121 Bonn (Germany)
2. Max Planck Institute for Brain Research, Deutschordenstr. 46, 60528 Frankfurt (Germany) and Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg (Germany)

Growing evidence shows that the soluble N-terminal form (sAPP{alpha}) of the amyloid precursor protein (APP) represents an epidermal growth factor fostering keratinocyte proliferation, migration and adhesion. APP is a member of a protein family including the two mammalian amyloid precursor-like proteins APLP1 and APLP2. In the mammalian epidermis, only APP and APLP2 are expressed. APP and APLP2-deficient mice die shortly after birth but do not display a specific epidermal phenotype. In this report, we investigated the epidermis of APP and/or APLP2 knockout mice. Basal keratinocytes showed reduced proliferation in vivo by about 40%. Likewise, isolated keratinocytes exhibited reduced proliferation rates in vitro, which could be completely rescued by either exogenously added recombinant sAPP{alpha}, or by co-culture with dermal fibroblasts derived from APP knockout mice. Moreover, APP-knockout keratinocytes revealed reduced migration velocity resulting from severely compromised cell substrate adhesion. Keratinocytes from double knockout mice died within the first week of culture, indicating essential functions of APP-family members for survival in vitro. Our data indicate that sAPP{alpha} has to be considered as an essential epidermal growth factor which, however, in vivo can be functionally compensated to a certain extent by other growth factors, e.g., factors released from dermal fibroblasts.

• OSTI ID: 20857990
• Journal Information: Experimental Cell Research, Vol. 312, Issue 11; Other Information: DOI: 10.1016/j.yexcr.2006.02.025; PII: S0014-4827(06)00071-1; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
EPIDERMIS
FIBROBLASTS
GROWTH FACTORS
IN VITRO
IN VIVO
KNOCK-OUT REACTIONS
MICE