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

Eun‐Mi Noh,Young‐Rae Lee,Kang‐Beom Kwon,Jeong‐Mi Kim,Hyun‐Kyung Song,On‐Yu Hong,Jong‐Suk Kim

doi:10.1111/jcmm.13220

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.

Highlights

Skin ageing can be divided into intrinsic or chronologic ageing, which is the process of senescence that affects all body organs, and extrinsic ageing, which occurs as a consequence of exposure to environmental factors [1, 2]
We generated an in vitro skin ageing model by replicative sub-culturing of human dermal fibroblasts (HDFs) cells isolated from foreskin
reactive oxygen species (ROS) play a major role in skin ageing by inducing chronological ageing and photoaging [23]

Summary

Introduction

Skin ageing can be divided into intrinsic or chronologic ageing, which is the process of senescence that affects all body organs, and extrinsic ageing (photoaging), which occurs as a consequence of exposure to environmental factors [1, 2]. ROS, primarily arising from oxidative cell metabolism, play a major role in both chronological ageing and photoaging [3]. The role of PTEN and NOX4 in replicative ageing-mediated MMP expression has not been determined. We investigated the effect of PTEN on replicative-induced MMP1 expression by increasing NOX4 and ROS generation.

Results

Conclusion