Universität zu Köln

Wegner, Jeannine, Loser, Karin, Apsite, Gunita, Nischt, Roswitha, Eckes, Beate, Krieg, Thomas, Werner, Sabine and Sorokin, Lydia (2016). Laminin alpha 5 in the keratinocyte basement membrane is required for epidermal-dermal intercommunication. Matrix Biol., 56. S. 24 - 42. AMSTERDAM: ELSEVIER. ISSN 1569-1802

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Abstract

Laminin alpha 5 is broadly expressed in the epidermal basement membrane (BM) of mature mice and its elimination at this site (Lama5(Ker5) mouse) results in hyperproliferation of basal keratinocytes and a delay in hair follicle development, which correlated with upregulation of the dermally-derived laminin alpha 2 and laminin alpha 4 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 alpha 5 does not result in cell autonomous defects in proliferation. Flow cytometry reveals that the loss of laminin alpha 5 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 alpha 5 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 alpha 5 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 Lama5(Ker5) skin, including KGF, EGF and KGF-2. In situ binding of FGF-receptor-2 alpha (111b)-Fc chimera (FGFR2111b) to mouse skin sections revealed decoration of several BMs, including the epidermal BM, which was absent in Lama5(Ker5) skin. This indicates reduced levels of FGFR2111b ligands, which include KGF and KGF-2, in the epidermal BM of adult Lama5(Ker5) skin. Our data suggest an initial inhibitory effect of laminin alpha 5 on basal keratinocyte proliferation and migration, which is exacerbated by subsequent changes in growth factor expression by epidermal and dermal cells, implicating laminin alpha 5 in epidermal dermal intercommunication. (C) 2016 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wegner, Jeannine UNSPECIFIED UNSPECIFIED UNSPECIFIED Loser, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Apsite, Gunita UNSPECIFIED UNSPECIFIED UNSPECIFIED Nischt, Roswitha UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Werner, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Sorokin, Lydia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-254172
DOI:	10.1016/j.matbio.2016.05.001
Journal or Publication Title:	Matrix Biol.
Volume:	56
Page Range:	S. 24 - 42
Date:	2016
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1569-1802
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language JUNCTIONAL EPIDERMOLYSIS-BULLOSA; HAIR FOLLICLE INDUCTION; EXTRACELLULAR-MATRIX; CHAIN GENE; TISSUE DISTRIBUTION; STEM-CELLS; EXPRESSION; BINDING; ADHESION; PROTEIN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25417