Investigation mechanisms between normal, developing and regenerating livers for regenerative liver drug design

Regen Med. 2019 May;14(5):359-387. doi: 10.2217/rme-2018-0058. Epub 2019 Jun 17.

Abstract

Aim: A systematic multimolecule drug design procedure is proposed for promoting hepatogenesis and liver regeneration. Materials & methods: Genome-wide microarray data including three hepatic conditions are obtained from the GEO database (GSE15238). System modeling and big data mining methods are used to construct real genome-wide genetic-and-epigenetic networks (GWGENs). Then, we extracted the core GWGENs by applying principal network projection on real GWGENs of normal, developing and regenerating livers, respectively. After that, we investigated the significant signal pathways and epigenetic modifications in the core GWGENs to identify potential biomarkers as drug targets. Result & conclusion: A multimolecule drug consisting of sulmazole, clofibrate, colchicine, furazolidone, nadolol, eticlopride and felbinac is proposed to target on novel biomarkers for promoting hepatogenesis and liver regeneration.

Keywords: big database analysis; development; epigenetics; hematopoiesis; hepatogenesis; liver; multimolecule drug; network biomarker; regeneration; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Data Mining*
  • Drug Design*
  • Epigenomics
  • Genome-Wide Association Study
  • Humans
  • Liver / metabolism*
  • Liver / pathology
  • Liver Regeneration / drug effects*
  • Pharmaceutical Preparations*

Substances

  • Biomarkers
  • Pharmaceutical Preparations