Estrogen receptor β signaling induces autophagy and downregulates Glut9 expression

Nucleosides Nucleotides Nucleic Acids. 2014;33(7):455-65. doi: 10.1080/15257770.2014.885045.

Abstract

Glut9 is highly expressed in the human kidney proximal convoluted tubular and plays a crucial role in the regulation of plasma urate levels. The gene effects were stronger among women. Our results show that 17-β-estradiol (E2) through ER (estrogen receptor) β downregulates Glut9 protein expression on human renal tubular epithelial cell line (HK2). Intriguingly, E2 does not affect the expression of Glut9 mRNA. ERβ is linked to PTEN, the PTEN gene negatively regulates the PI3K/AKT pathway, and the PI3K/AKT pathway inhibition may lead to autophagy. Further study indicates that ERβ may affect the expression of Glut9 though autophagy.

Keywords: Phosphorylases; gene regulation; mechanism of action studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy* / drug effects
  • Cell Line
  • Down-Regulation* / drug effects
  • Estradiol / pharmacology
  • Estrogen Receptor beta / metabolism*
  • Glucose Transport Proteins, Facilitative / genetics*
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Humans
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proteolysis / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction* / drug effects

Substances

  • Estrogen Receptor beta
  • Glucose Transport Proteins, Facilitative
  • RNA, Messenger
  • SLC2A9 protein, human
  • Estradiol
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase