title: Laminin α5 in the keratinocyte basement membrane is required for epidermal-dermal intercommunication.
abstract: Laminin α5 is broadly expressed in the epidermal basement membrane (BM) of mature mice and its elimination at this site (Lama5Ker5mouse) results in hyperproliferation of basal keratinocytes and a delay in hair follicle development, which correlated with upregulation of the dermally-derived laminin α2 and laminin α4 chains in the epidermal BM and of tenascin-C subjacent to the BM. In vitro studies revealed laminin 511 to be strongly adhesive for primary keratinocytes and that loss of laminin α5 does not result in cell autonomous defects in proliferation. Flow cytometry reveals that the loss of laminin α5 resulted in increased numbers of CD45+, CD4+and CD11b+immune cells in the skin, which temporo-spatial analyses revealed were detectable only subsequent to the loss of laminin α5 and the appearance of the hyperproliferative keratinocyte phenotype. These findings indicate that immune cell changes are the consequence and not the cause of keratinocyte hyperproliferation. Loss of laminin α5 in the epidermal BM was also associated with changes in the expression of several dermally-derived growth factors involved in keratinocyte proliferation and hair follicle development in adult but not new born Lama5Ker5skin, including KGF, EGF and KGF-2. In situ binding of FGF-receptor-2α (IIIb)-Fc chimera (FGFR2IIIb) to mouse skin sections revealed decoration of several BMs, including the epidermal BM, which was absent in Lama5Ker5skin. This indicates reduced levels of FGFR2IIIb ligands, which include KGF and KGF-2, in the epidermal BM of adult Lama5Ker5skin. Our data suggest an initial inhibitory effect of laminin α5 on basal keratinocyte proliferation and migration, which is exacerbated by subsequent changes in growth factor expression by epidermal and dermal cells, implicating laminin α5 in epidermal-dermal intercommunication.
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany.
authors.forename: Jeannine
authors.initials: J
authors.lastname: Wegner
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Germany; Department of Dermatology, University of Muenster, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany.
authors.forename: Gunita
authors.initials: G
authors.lastname: Apsite
authors.affiliation: Department of Dermatology, University of Cologne, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
authors.affiliation: Department of Dermatology, University of Cologne, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.affiliation: Department of Dermatology, University of Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany. Electronic address: sorokin@uni-muenster.de.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D005260:Female; D015603:Keratinocytes / Q000502:physiology*; D007797:Laminin / Q000502:physiology*; D008297:Male; D018345:Mice, Knockout
chemical_list: D007797:Laminin; C097043:laminin alpha5
keywords: Basement membrane; Epithelial–mesenchymal interactions; Keratinocytes; Laminin