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

Eun-Mi Noh1, Jeong-Mi Kim1, On-Yu Hong2

  • 1Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan City, Jeonbuk, South Korea.

Insights

Reactive oxygen species (ROS) drive skin aging by increasing matrix metalloproteinase-1 (MMP-1) expression. PTEN gene transfer inhibited this process, suggesting a link between PTEN, NOX, and ROS in skin aging.

Area of Science:

  • Biochemistry
  • Dermatology
  • Cell Biology

Background:

  • NADPH oxidase (NOX) generates reactive oxygen species (ROS), implicated in skin aging.
  • ROS contribute to chronological and photoaging, potentially inducing matrix metalloproteinase (MMP) expression.
  • NADPH oxidase signaling is linked to PI3K and PKC pathways, but PTEN and NOX4 roles in aged MMP expression are unclear.

Purpose of the Study:

  • To investigate the role of PTEN and NOX4 in replicative-aged MMP expression.
  • To determine the relationship between PTEN, NOX4, ROS, and MMP-1 in aged skin cells.

Main Methods:

  • PTEN gene transfer to inhibit the PI3K signaling pathway.
  • NOX-4 down-expression in replicative-aged skin cells.
  • Measurement of NOX-4, MMP-1 expression, and ROS generation.

Main Results:

  • PTEN gene transfer abolished NOX-4 and MMP-1 expression.
  • NOX-4 down-expression in aged skin cells reduced MMP-1 expression and ROS generation.
  • Replicative-induced ROS increase MMP-1 expression, linked to altered PTEN and NOX expression.

Conclusions:

  • PTEN inhibition of PI3K signaling impacts NOX-4 and MMP-1 expression.
  • NOX-4 is crucial for ROS generation and MMP-1 expression in aged skin cells.
  • Changes in PTEN and NOX expression are associated with increased MMP-1 due to ROS in replicative aging.

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