Emodin-mediated cross-linking enhancement for extracellular matrix homeostasis

Biochem Biophys Res Commun. 2014 Apr 18;446(4):1022-8. doi: 10.1016/j.bbrc.2014.03.052. Epub 2014 Mar 26.

Abstract

The extracellular matrix (ECM) is an essential element of mammalian organisms, and its cross-linking formation plays a vital role in ECM development and postnatal homeostasis. Defects in cross-link formation caused by aging, genetic, or environmental factors are known to cause numerous diseases in mammals. To augment the cross-linking formation of ECM, the present study established a ZsGreen reporter system controlled by the promoter of lysyl oxidase-like 1 gene (LOXL1), which serves as both a scaffold element and a cross-linking enzyme in the ECM. By using this system in a drug screen, we identified emodin as a strong enhancer of LOXL1 expression that promoted cross-linking formation of ECM in all the tested systems, including human fibroblast cells, cultured human skin tissues, and animals that received long-term emodin treatment. Collectively, the results suggest that emodin may serve as an effective drug or supplement for ECM homeostasis.

Keywords: Cross-linking; Emodin; Extracellular matrix (ECM); Lysyl oxidase-like 1 (LOXL1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism*
  • Animals
  • Cell Line
  • Desmosine / metabolism
  • Elastin / metabolism
  • Emodin / pharmacology*
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Homeostasis / drug effects
  • Humans
  • Hydroxyproline / metabolism
  • Promoter Regions, Genetic / drug effects
  • Protein Kinase Inhibitors / pharmacology*
  • Up-Regulation

Substances

  • Protein Kinase Inhibitors
  • Desmosine
  • Elastin
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human
  • Emodin
  • Hydroxyproline