140 Microarray Expression Analysis of Fetal Mouse Skin Development: Implications for Scarless Healing

Abstract

Introduction: Fetal mouse skin wounds heal without scar before gestational day E17. Because scarless repair is inherent to fetal skin and occurs superimposed on skin differentiation, genome‐wide gene expression during skin development was tested. Methods: Dorsal skin from BALB/C mice fetuses at E14, E15, E18 and E20 was collected. RNAs from individual fetuses were hybridized to mouse microarrays with 42,000 gene elements. The E14/E18 hybridizations were repeated three times, and the E15/E20 repeated twice with different samples. (“x” = fold change). Results: Increased genes on E18 and E20 were clustered into several groups: 1) ECMs: type I (2.8x), III (2.3x), VI, and XIV procollagens; 2) Cell surface: integrin beta1 binding protein2 (5.2x), integral membrane protein2A and 2B (avg 3.8x); 3) Proteases: mast cell protease4 (15x) and 5 (24x), MMP23 (3x); 4) Growth factor‐related: acidic FGF (3.7x), FGF receptor3 (2.9x), TGF‐alpha (2.3x).Decreased genes on E18 and E20 included: 1) Growth factors: TGF‐beta2 (0.42x), PDGF‐alpha (0.41x), PDGF receptor‐beta (0.37x), NGF receptor associated protein (0.18x); 2) Proteases: MMP 11 (0.27x), 14 (0.39x); 3) ECM: fibromodulin (0.5x), Vcam1 (0.22x), keratin18 (0.2x) and 19 (0.46x), collagen XVIII (0.36x). Conclusions: Genes with increased expression at E14, E15 and decreased expression at E18, E20 have possible antifibrotic function. These data identify hundreds of possible anti‐fibrotic and pro‐fibrotic genes as candidates for further functional analysis as regulators of repair.Supported by NIH DE00463–03