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.
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.
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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