PTEN inhibits replicative senescence-induced MMP-1 expression by regulating NOX4-mediated ROS in human dermal fibroblasts

J Cell Mol Med. 2017 Nov;21(11):3113-3116. doi: 10.1111/jcmm.13220. Epub 2017 May 30.

Abstract

The biological function of NADPH oxidase (NOX) is the generation of reactive oxygen species (ROS). ROS, primarily arising from oxidative cell metabolism, play a major role in both chronological ageing and photoageing. ROS in extrinsic and intrinsic skin ageing may be assumed to induce the expression of matrix metalloproteinases. NADPH oxidase is closely linked with phosphatidylinositol 3-OH kinase (PI3K) signalling. Protein kinase C (PKC), a downstream molecule of PI3K, is essential for superoxide generation by NADPH oxidase. However, the effect of PTEN and NOX4 in replicative-aged MMPs expression has not been determined. In this study, we confirmed that inhibition of the PI3K signalling pathway by PTEN gene transfer abolished the NOX-4 and MMP-1 expression. Also, NOX-4 down-expression of replicative-aged skin cells abolished the MMP-1 expression and ROS generation. These results suggest that increase of MMP-1 expression by replicative-induced ROS is related to the change in the PTEN and NOX expression.

Keywords: PTEN; reactive oxygen species; MMP-1; NADPH oxidase-4; skin ageing.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Cells, Cultured
  • Cellular Senescence / genetics*
  • Dermis / cytology
  • Dermis / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 1 / metabolism
  • NADPH Oxidase 4 / antagonists & inhibitors
  • NADPH Oxidase 4 / genetics*
  • NADPH Oxidase 4 / metabolism
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Transfection

Substances

  • RNA, Small Interfering
  • Reactive Oxygen Species
  • NADPH Oxidase 4
  • NOX4 protein, human
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase C
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • MMP1 protein, human
  • Matrix Metalloproteinase 1