| First Author | Siemes C | Year | 2006 |
| Journal | Exp Cell Res | Volume | 312 |
| Issue | 11 | Pages | 1939-49 |
| PubMed ID | 16584729 | Mgi Jnum | J:111366 |
| Mgi Id | MGI:3653813 | Doi | 10.1016/j.yexcr.2006.02.025 |
| Citation | Siemes C, et al. (2006) Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro. Exp Cell Res 312(11):1939-49 |
| abstractText | Growing evidence shows that the soluble N-terminal form (sAPPalpha) 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 sAPPalpha, 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 sAPPalpha 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. |
