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Microarray‐based identification of aminopeptidase N target genes in keratinocyte conditioned medium‐stimulated dermal fibroblasts
Author(s) -
Lai Amy,
Ghaffari Abdi,
Li Yunyuan,
Ghahary Aziz
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23438
Subject(s) - tenascin c , fibronectin , fibroblast , extracellular matrix , microbiology and biotechnology , dermal fibroblast , wound healing , tenascin , matrix metalloproteinase , chemistry , keratinocyte , microarray analysis techniques , downregulation and upregulation , gene expression , biology , cell culture , immunology , gene , biochemistry , genetics
Of the many processes that affect the outcome of wound repair, epidermal–dermal interactions are essential to extracellular matrix (ECM) remodeling and in particular, soluble factors released by keratinocytes are known to have a direct impact on the production of ECM by dermal fibroblasts. Aminopeptidase N (APN) has recently been proposed as a cell‐surface receptor for stratifin and is responsible for the stratifin‐mediated matrix metalloproteinase‐1 (MMP‐1) upregulation in fibroblasts. The present study examines whether modulation of APN gene expression has any impact on the fibroblast ECM gene expression profile. The result reveals that in the presence of keratinocyte‐derived soluble factors, transient knockdown of APN in dermal fibroblasts affects the expression of key ECM components such as fibronectin, tenascin‐C, MMP‐1, MMP‐3, and MMP‐12. The regulatory effects of APN on fibronectin and selective MMPs appear to be associated with receptor‐mediated signal transduction independently of its peptidase activity. On the contrary, inhibition of the APN enzymatic activity by bestatin significantly reduces the tenascin‐C expression and enhances the contraction of fibroblast‐populated collagen gel, suggesting an activity‐dependent regulation of fibroblast contractility by APN. The overall effects of APN on the expression of fibronectin, tenascin‐C, and MMPs in fibroblasts propose an important role for APN in the regulation of keratinocyte‐mediated ECM remodeling and fibroblast contractile activity. J. Cell. Biochem. 113: 1061–1068, 2012. © 2011 Wiley Periodicals, Inc.