GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation‑induced photoaging of human skin fibroblast cells

Qin, Haiyan; Guang, Zhang; Zhang, Lianbo

doi:10.3892/etm.2018.5863

Cited by 8 publications

(9 citation statements)

References 41 publications

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“…Another significant finding of our study was that the silencing of PVT1 or the upregulation of FOXA1 can inhibit the apoptosis and damage of podocytes, while GSK126, an EZH2 inhibitor, can reverse the damage and apoptosis of podocytes in DN. GSK126, a methyltransferase activity inhibitor, has been shown to selectively suppress the activity of EZH2-methyltransferase as well as EZH2 gene expression 20 . It has been reported that PVT1, which is highly expressed in DN podocytes, is induced by HG and is involved in the accumulation of extracellular matrix 7 .…”

Section: Discussionmentioning

confidence: 99%

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

Zhang

Liu

et al. 2019

Exp Mol Med

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The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance.

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Section: Discussionmentioning

confidence: 99%

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

Zhang

Liu

et al. 2019

Exp Mol Med

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“…Cellular senescence is characterized by the oxidative stress that results from the accumulation of ROS and lysosome content [28]. We conducted a CM-H 2 DCFDA staining assay using flow cytometry to assess whether ES-GNPs could effectively inhibit the intracellular ROS production in UVA-irradiated HDFs.…”

Section: Es-gnps Inhibit Ros Production and Lysosome Content In Uva-imentioning

confidence: 99%

Gold Nanoparticles Using Ecklonia stolonifera Protect Human Dermal Fibroblasts from UVA-Induced Senescence through Inhibiting MMP-1 and MMP-3

Jun

Kim

et al. 2020

Marine Drugs

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The effect of gold nanoparticles (GNPs) synthesized in marine algae has been described in the context of skin, where they have shown potential benefit. Ecklonia stolonifera (ES) is a brown algae that belongs to the Laminariaceae family, and is widely used as a component of food and medicine due to its biological activities. However, the role of GNPs underlying cellular senescence in the protection of Ecklonia stolonifera gold nanoparticles (ES-GNPs) against UVA irradiation is less well known. Here, we investigate the antisenescence effect of ES-GNPs and the underlying mechanism in UVA-irradiated human dermal fibroblasts (HDFs). The DPPH and ABTS radical scavenging activity of ES extracts was analyzed. These analyses showed that ES extract has potent antioxidant properties. The facile and optimum synthesis of ES-GNPs was established using UV-vis spectra. The surface morphology and crystallinity of ES-GNPs were demonstrated using high resolution transmission electron microscopy (HR-TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). ES-GNPs presented excellent photocatalytic activity, as shown by the photo-degradation of methylene blue and rhodamine B. A cellular senescence model was established by irradiating HDFs with UVA. UVA-irradiated HDFs exhibited increased expression of senescence-associated β-galactosidase (SA-β-galactosidase). However, pretreatment with ES-GNPs resulted in reduced SA-β-galactosidase activity in UVA-irradiated HDFs. Intracellular ROS levels and G1 arrest in UVA-irradiated HDFs were checked against the background of ES-GNP treatment to investigate the antisenescence effects of ES-GNPs. The results showed that ES-GNPs significantly inhibit UVA-induced ROS levels and G1 arrest. Importantly, ES-GNPs significantly downregulated the transcription and translation of MMP (matrix metalloproteinases)-1/-3, which regulate cellular senescence in UVA-irradiated HDFs. These findings indicate that our optimal ES-GNPs exerted an antisenescence effect on UVA-irradiated HDFs by inhibiting MMP-1/-3 expression. Collectively, we posit that ES-GNPs may potentially be used to treat photoaging of the skin.

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“…Photoaging reduces the amount of mature type I collagen and elastic fibers in the dermis of the skin. The clinical characteristics of photoaging occur mainly on exposed skin, such as the face, neck, and forearm, where rough skin, loss of elasticity, deepening and thickening of wrinkles, a leather-like appearance, pigmentation, and dilated capillaries can occur ( Qin et al, 2018 ). Studies have shown that approximately 65% of patients with melanoma and 90% of patients with non-melanoma skin cancers, including BCC and SCC, are associated with skin photoaging ( Damiani and Ullrich, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway

Zhou

et al. 2021

Front. Pharmacol.

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Long-term exposure to UVB (280–320 nm) can cause oxidative skin damage, inflammatory injury, and skin cancer. Research on nicotinamide mononucleotide (NMN) and lactic acid bacteria (LAB) with regard to antioxidation, anti-inflammation, and prevention of other age-related diseases has received increasing attention. In the present study, the in vitro antioxidant analysis showed that NMN combined with Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) has a high scavenging ability on hydroxyl (OH), 2, 2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and it also possess a good total antioxidant capacity. The animal experimental results show that NMN combined with LAB maintained normal liver morphology of mice and reduced pathological damage to murine skin. NMN combined with LAB significantly increased the serum levels of total superoxide dismutase (T-SOD), catalase (CAT), and interleukin (IL)-10, but reduced the levels of malondialdehyde, advanced glycation end products, tumor necrosis factor (TNF)-α, and IL-6. NMN combined with LAB increased T-SOD, CAT, IL-10, Na+-K+-ATPase, and NAD+ levels in the skin, but reduced TNF-α level in the skin. NMN combined with LAB increased the mRNA expression levels of SOD1, CAT, glutathione (GSH), inhibitor of NF-κB (IκB-α), IL-10, AMP-activated protein kinase (AMPK), adaptor protein, phosphotyros ineinteraction, PH domain and leucine zipper containing 1 (APPL1), peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), and forkhead transcription factor O (FOXO) in the skin and liver, but decreased the mRNA expression levels of nuclear factor (NF)-κBp65, TNF-α, IL-6, and rapamycin target protein (mTOR). NMN combined with LAB increased the protein expression levels of AMPK, IκB-α, SOD1, and CAT in the skin tissues and reduced protein expression of NF-κBp65. NMN combined with L. fermentum TKSN041 improved murine skin damage caused by UVB irradiation, and the protective mechanism may be related to activation of the AMPK signaling pathway. The results of this study are expected to provide a reference for preventing and the treating skin photoaging.

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GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation‑induced photoaging of human skin fibroblast cells

Cited by 8 publications

References 41 publications

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

Gold Nanoparticles Using Ecklonia stolonifera Protect Human Dermal Fibroblasts from UVA-Induced Senescence through Inhibiting MMP-1 and MMP-3

Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway

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