title: Paracrine regulation of fibroblast aminopeptidase N/CD13 expression by keratinocyte-releasable stratifin.
abstract: As wound healing proceeds into the tissue remodeling phase, cellular interactions become dominated by the interplay of keratinocytes with fibroblasts in the skin, which is largely mediated through paracrine signaling and greatly affects the molecular constitution of the extracellular matrix. We have recently identified aminopeptidase N (APN)/CD13 as a potential fibroblast receptor for 14-3-3 sigma (also known as stratifin), a keratinocyte-releasable protein with potent matrix metalloproteinase 1 (MMP1) stimulatory activity. The present study demonstrates that the expression of APN on dermal fibroblasts is regulated through paracrine signaling by keratinocyte-derived soluble factors. By using an in vitro keratinocyte-fibroblast co-culture system, we showed that APN expression in dermal fibroblasts is induced in the presence of keratinocytes or in response to keratinocyte-conditioned medium. Conditioned medium collected from differentiated keratinocytes further increases APN protein production, suggesting an amplified stimulatory effect by keratinocyte differentiation. Recombinant stratifin potently induces APN synthesis in a dose-dependent manner. A consistent correlation between the protein expression levels of APN and MMP1 was also observed. These results confirm paracrine regulation of APN expression in dermal fibroblasts by keratinocyte-derived stimuli, in particular stratifin, and provide evidence that APN may serve as a target in the regulation of MMP1 expression in epidermal-mesenchymal communication.
authors.affiliation: BC Professional Fire Fighters' Burn and Wound Healing Laboratory, Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Lai
authors.forename: Abdi
authors.initials: A
authors.lastname: Ghaffari
authors.forename: Yunyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019899:Paracrine Communication; D011480:Protease Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex