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Artesunate inhibits myofibroblast formation via induction of apoptosis and antagonism of pro-fibrotic gene expression in human dermal fibroblasts.
Larson, Sara A; Dolivo, David M; Dominko, Tanja.
Affiliation
  • Larson SA; Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609, USA.
  • Dolivo DM; Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609, USA.
  • Dominko T; Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609, USA.
Cell Biol Int ; 43(11): 1317-1322, 2019 Nov.
Article in En | MEDLINE | ID: mdl-31441159
ABSTRACT
The anti-malaria drug artesunate and other chemical analogs of artemisinin have demonstrated cytostatic and cytotoxic effects in bacterial and cancer cells. Artemisinin-derived compounds have also been demonstrated to attenuate fibrosis in preclinical animal models, but the mechanisms by which this inhibition occurs are not well-understood. We investigated the effects of artesunate on the emergence of the myofibroblast, which is causally implicated in pro-fibrotic pathologies. CRL-2097 human dermal fibroblasts were analyzed for protein and transcript expression after treatment with artesunate to analyze fibroblast activation. Proliferation and apoptosis were also evaluated following treatment with artesunate in this cell line. Treatment of human dermal fibroblasts with artesunate antagonized fibroblast activation and pro-fibrotic extracellular matrix (ECM) deposition, both at basal culture conditions and when cultured in the presence of exogenous transforming growth factor-ß1 (TGF-ß1), a major pro-fibrotic cytokine. Artesunate-treated fibroblasts also demonstrated decreased proliferation and increased apoptosis. Transcript analysis by quantitative real-time polymerase chain reaction demonstrated that artesunate downregulated expression of pro-fibrotic genes including canonical myofibroblast markers, ECM genes, and several TGF-ß receptors and ligands, and upregulated expression of cell cycle inhibitors and matrix-metalloproteinases. Together, these data demonstrate that artesunate antagonizes fibroblast activation and decreases expression of pro-fibrotic genes, while also promoting myofibroblast apoptosis, suggesting that these mechanisms may be responsible in part for the anti-fibrotic effects of artesunate described previously.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin / Transforming Growth Factor beta1 / Myofibroblasts / Artesunate Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cell Biol Int Year: 2019 Type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin / Transforming Growth Factor beta1 / Myofibroblasts / Artesunate Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cell Biol Int Year: 2019 Type: Article Affiliation country: United States