Abstract
Hypertrophic scars (HS) limit movement, decrease quality of life, and remain a major impediment to rehabilitation from burns. However, no effective pharmacologic therapies for HS exist. Here we tested the in vitro anti-fibrotic effects of the novel chemical N-(2-aminoethyl) ethanolamine (AEEA) at non-toxic concentrations. Scanning electron microscopy showed that AEEA markedly altered the structure of the extracellular matrix (ECM) produced by primary dermal fibroblasts isolated from a HS of a burn patient (HTS). Compression atomic force microscopy revealed that AEEA stiffened the 3D nanostructure of ECM formed by HTS fibroblasts. Western blot analysis in three separate types of primary human dermal fibroblasts (including HTS) showed that AEEA exposure increased the extractability of type I collagen in a dose- and time-dependent fashion, while not increasing collagen synthesis. A comparison of the electrophoretic behavior of the same set of samples under native and denaturing conditions suggested that AEEA alters the 3D structure of type I collagen. The antagonization effect of AEEA to TGF-β1 on ECM formation was also observed. Furthermore, analyses of the anti-fibrotic effects of analogs of AEEA (with modified pharmacophores) suggest the existence of a chemical structure-activity relationship. Thus, AEEA and its analogs may inhibit HS development; further study and optimization of analogs may be a promising strategy for the discovery for effective HS therapies.