<scp>NADPH</scp> oxidase is a novel target of delphinidin for the inhibition of <scp>UVB</scp>‐induced <scp>MMP</scp>‐1 expression in human dermal fibroblasts

Lim, Tae‐Gyu; Jung, Sung Keun; Kim, Jong‐Eun; Kim, Yoona; Lee, Hyong Joo; Jang, Tae Su; Lee, Ki Won

doi:10.1111/exd.12157

Cited by 40 publications

(29 citation statements)

References 20 publications

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“…Accordingly, in this study, we investigated the ROS generation signalling pathway in replicative‐aged skin cells. Previous reports have demonstrated that increasing ROS levels in HDFs lead to the upregulation of MMP expression . Therefore, in this study, we confirmed that the expression of MMPs increased in replicative‐aged HDF cells (Fig.…”

Section: Resultssupporting

confidence: 88%

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

Noh

Kim

Hong

et al. 2017

J Cellular Molecular Medi

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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.

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Section: Resultssupporting

confidence: 88%

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

Noh

Kim

Hong

et al. 2017

J Cellular Molecular Medi

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“…The primary reason for the loss of skin barrier integrity and tissue erosion, associated with acute exposure to UV‐B irradiation, is the generation of ROS . Elevated ROS disturbs equilibrium between pro‐ and antioxidants in the cell and activates various intracellular signalling pathways, leading to photodamage . Therefore, new strategies to ameliorate UV‐B‐induced damage deserve examination.…”

Section: Discussionmentioning

confidence: 99%

Glycyrrhizic acid prevents ultraviolet‐B‐induced photodamage: a role for mitogen‐activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway

Afnan

Kaiser

Rafiq

et al. 2016

Experimental Dermatology

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Glycyrrhizic acid (GA), a natural triterpene, has received attention as an agent that has protective effects against chronic diseases including ultraviolet UV-B-induced skin photodamage. However, the mechanism of its protective effect remains elusive. Here, we used an immortalized human keratinocyte cell line (HaCaT) and a small animal model (BALB/c mice), to investigate the protective effects of GA against UV-B-induced oxidative damage, and additionally, delineated the molecular mechanisms involved in the UV-B-mediated inflammatory and apoptotic response. In the HaCaT cells, GA inhibited the UV-B-mediated increase in intracellular reactive oxygen species (ROS) and down-regulated the release of pro-inflammatory cytokines interleukin (IL)-1α, -1β and -6, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2). GA inhibited UV-B-mediated activation of p38 and JNK MAP kinases, COX-2 expression and nuclear translocation of NF-κB. Furthermore, GA inhibited UV-B-mediated apoptosis by attenuating translocation of Bax from the cytosol to mitochondria, thus preserving mitochondrial integrity. GA-treated HaCaT cells also exhibited elevated antiapoptotic Bcl-2 protein, concomitant with reduced caspase-3 cleavage and decreased PARP-1 protein. In BALB/c mice, topical application of GA on dorsal skin exposed to UV-B irradiation protected against epidermal hyperplasia, lymphocyte infiltration and expression of several inflammatory proteins, p38, JNK, COX-2, NF-κB and ICAM-1. Based on the above findings, we conclude that GA protects against UV-B-mediated photodamage by inhibiting the signalling cascades triggered by oxidative stress, including MAPK/NF-κB activation, as well as apoptosis. Thus, GA has strong potential to be used as a therapeutic/cosmeceutical agent against photodamage.

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“…In addition, dermal fibroblasts also produce ROS via NOXs in response to growth factors . Recently, NADPH oxidase was characterised as a novel target of delphinidin in the inhibition of UVB‐induced MMP‐1 expression in human dermal fibroblasts .…”

Section: Introductionmentioning

confidence: 99%

NADPH oxidase‐2 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis

Zhang

Dai

et al. 2014

Experimental Dermatology

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The proliferation of human skin dermal fibroblasts (HDFs) is a critical step in skin fibrosis, and transforming growth factor-beta1 (TGF-β1) exerts pro-oxidant and fibrogenic effects on HDFs. In addition, the oxidative stress system has been implicated in the pathogenesis of skin disease. However, the role of NADPH oxidase as a mediator of TGF-β1-induced effects in HDFs remains unknown. Thus, our aim was to investigate the role of NADPH in human skin dermal fibroblasts. Primary fibroblasts were cultured and pretreated with various stimulants. Real-time Q-PCR and Western blotting analyses were used for mRNA and protein detection. In addition, siRNA technology was applied for gene knock-down analysis. Hydrogen peroxide production and 2',7'-dichlorofluorescein diacetate (DCFDA) measurement assay were performed. Here, our findings demonstrated that HDFs express key components of non-phagocytic NADPH oxidase mRNA. TGF-β1 induced NOX2 and reactive oxygen species formation via NADPH oxidase activity. In contrast, NOX3 was barely detectable, and other NOXs did not display significant changes. In addition, TGF-β1 phosphorylated MAPKs and increased activator protein-1 (AP-1) in a redox-sensitive manner, and NOX2 suppression inhibited baseline and TGF-β1-mediated stimulation of Smad2 phosphorylation. Moreover, TGF-β1 stimulated cell proliferation, migration, collagen I and fibronectin expression, and bFGF and PAI-1 secretion: these effects were attenuated by diphenylene iodonium (DPI), an NADPH oxidase inhibitor, and NOX2 siRNA. Importantly, NOX2 siRNA suppresses collagen production in primary keloid dermal fibroblasts. These findings provide the proof of concept for NADPH oxidase as a potential target for the treatment of skin fibrosis.

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NADPH oxidase is a novel target of delphinidin for the inhibition of UVB‐induced MMP‐1 expression in human dermal fibroblasts

Cited by 40 publications

References 20 publications

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

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

Glycyrrhizic acid prevents ultraviolet‐B‐induced photodamage: a role for mitogen‐activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway

NADPH oxidase‐2 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis

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