PI3K/Akt pathway mediates high glucose-induced lipogenesis and extracellular matrix accumulation in HKC cells through regulation of SREBP-1 and TGF-β1

Histochem Cell Biol. 2011 Feb;135(2):173-81. doi: 10.1007/s00418-011-0777-3. Epub 2011 Jan 15.

Abstract

Previous studies have shown that high glucose stimulates renal SREBP-1 gene expression and increases renal tubular cells lipid metabolism, however, the mechanisms remain elusive. In the present study we demonstrated that PI3K/Akt pathway was activated in human renal proximal tubular cell line (HKC) exposed to high glucose accompanied with up-regulation of SREBP-1, TGF-β1, lipid droplets deposits and extracellular matrix production. Inhibition of PI3K/Akt pathway by chemical LY294002 or specific short hairpin RNA (shRNA) vector prevented SREBP-1 and TGF-β1 up-regulation, as well as ameliorated HKC cells lipogenesis and extracellular matrix accumulation. These findings indicate that PI3K/Akt pathway potentially mediates high glucose-induced lipogenesis and extracellular matrix accumulation in HKC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromones / pharmacology
  • Extracellular Matrix / metabolism*
  • Glucose / administration & dosage
  • Glucose / pharmacology*
  • Humans
  • Kidney Tubules, Proximal / metabolism
  • Lipogenesis / genetics*
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / metabolism*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Chromones
  • Morpholines
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Transforming Growth Factor beta1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Glucose