Basement membrane reconstruction in human skin equivalents is regulated by fibroblasts and/or exogenously activated keratinocytes.
This study was undertaken to examine the role fibroblasts play in the formation of the basement membrane (BM) in human skin equivalents. For this purpose, keratinocytes were seeded on top of fibroblast-free or fibroblast-populated collagen matrix or de-epidermized dermis and cultured in the absence of serum and exogenous growth factors. The expression of various BM components was analyzed on the protein and mRNA level. Irrespective of the presence or absence of fibroblasts, keratin 14, hemidesmosomal proteins plectin, BP230 and BP180, and integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta4 were expressed but laminin 1 was absent. Only in the presence of fibroblasts or of various growth factors, laminin 5 and laminin 10/11, nidogen, uncein, type IV and type VII collagen were decorating the dermal/epidermal junction. These findings indicate that the attachment of basal keratinocytes to the dermal matrix is most likely mediated by integrins alpha1beta1 and alpha2beta1, and not by laminins that bind to integrin alpha6beta4 and that the epithelial-mesenchymal cross-talk plays an important role in synthesis and deposition of various BM components.
El Ghalbzouri
Abdoelwaheb
A
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Jonkman
Marcel F
MF
Dijkman
Remco
R
Ponec
Maria
M
D000941:Antigens / Q000378:metabolism; D001485:Basement Membrane / Q000166:cytology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D024143:Collagen Type VII / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003896:Desmosomes / Q000378:metabolism; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000502:physiology*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism; D039201:Integrin alpha3beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D009924:Organ Culture Techniques; D000097794:Kalinin
D000941:Antigens; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D024143:Collagen Type VII; D004815:Epidermal Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D039201:Integrin alpha3beta1; D007797:Laminin; D000097794:Kalinin; C089136:19-DEJ-1 antigen; C496453:FGF7 protein, human; C119013:laminin 10; C474559:laminin 11 protein, human