Artesunate-induced antagonism of fibrotic gene expression and attenuation of myofibroblast-associated phenotypes

Larson, Sara Aristia

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Artesunate-induced antagonism of fibrotic gene expression and attenuation of myofibroblast-associated phenotypes

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Antimalarial artemisinin-derived compounds have attenuated fibrosis in preclinical 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 causes fibrosis. Treatment of human dermal fibroblasts with artesunate antagonized fibroblast activation and ECM deposition. Artesunate-treated fibroblasts demonstrated decreased proliferation and increased apoptosis. qRT-PCR analysis showed artesunate-mediated downregulation of profibrotic genes, and upregulated expression of growth inhibitors and MMPs. These data suggest that the antifibrotic mechanisms of artesunate may be mediated by antagonistic effects towards profibrotic gene expression, and by induction of myofibroblast apoptosis.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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