A chemical screen identifies small molecules that regulate hepcidin expression
Ferroportin
Viability assay
DOI:
10.1016/j.bcmd.2014.06.002
Publication Date:
2014-07-04T03:45:32Z
AUTHORS (7)
ABSTRACT
Hepcidin, a peptide hormone produced in the liver, decreases intestinal iron absorption and macrophage release via effects on ferroportin. Bone morphogenic protein Stat3 signaling regulate Hepcidin's transcription. Hepcidin is potential drug target for patients with overload syndromes because its levels are inappropriately low these individuals. To generate tool identifying small molecules that modulate expression, we stably transfected human hepatocytes (HepG2) cells reporter construct containing 2.7 kb of promoter upstream firefly gene. We used high throughput methods to screen 10,169 chemicals duplicate their effect expression cell viability. Regulators were identified as caused change > 3 standard deviations above or 1 deviation below mean other (z-score < 1), while not adversely affecting viability, quantified by fluorescence assay. Following validation assays, 16 broad range functional classes promote expression. All increased bone protein-dependent and/or Stat3-dependent genes, however none them strongly phosphorylation Smad1,5,8 Stat3.
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