Effect of N-(2-aminoethyl) ethanolamine on hypertrophic scarring changes in vitro: Finding novel anti-fibrotic therapies
| Autor: | Celeste C. Finnerty, Jianhua Gu, Amina El Ayadi, Paul J. Boor, Linda E. Sousse, Zhenping Chen, David N. Herndon, Jia Zhou, Andres F. Oberhauser |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Anti fibrotic Cicatrix Hypertrophic Toxicology Article Cell Line Transforming Growth Factor beta1 Extracellular matrix Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ethanolamine Western blot medicine Humans Pharmacology medicine.diagnostic_test Fibroblasts Fibrosis Molecular biology In vitro Extracellular Matrix 030104 developmental biology chemistry Ethanolamines 030220 oncology & carcinogenesis Hypertrophic scarring Collagen Wound healing Type I collagen |
| Zdroj: | Toxicology and Applied Pharmacology. 362:9-19 |
| ISSN: | 0041-008X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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