Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1 and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts

Lu, Jing; Guo, Jiahui; Tu, Xue-Liang; Zhang, Chao; Zhao, Ming; Zhang, Quanwu; Gao, Feng‐Hou

doi:10.1371/journal.pone.0159998

Cited by 67 publications

(55 citation statements)

References 42 publications

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“…UV radiation activates cell surface receptors, causing protein kinase cascades of MAPK and AP-1, resulting in the expression of MMPs (36). As expected, C-Mx inhibited UVB-induced phosphorylation of ERK, JNK, and p38, which act up-stream of AP-1.…”

Section: Discussionsupporting

confidence: 73%

Ginsenoside C‐Mx Isolated from Notoginseng Stem‐leaf Ginsenosides Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts

Liu

Hwang

Park

et al. 2018

Photochem & Photobiology

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Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create a reaction with the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1 and IL-6 expression while accelerating TGF-β and procollagen type I secretion. In addition, ginsenoside C-Mx reversed UVB-induced procollagen type I reduction by regulating the TGF-β/Smad signaling pathway. Moreover, ginsenoside C-Mx inhibited activation of AP-1 transcription factor, an inducer of MMPs. Ginsenoside C-Mx displayed an outstanding antioxidant capacity, increasing expression of cytoprotective antioxidants such as HO-1 and NQO-1 expression by enhancing the nuclear accumulation of Nrf2. Interestingly, application of ginsenoside C-Mx treatment (1, 10, 20 μm) significantly diminished UVB-induced suppressed NF-κB expression, decreasing the over-released inflammatory cytokines. Taken together, our findings indicated that ginsenoside C-Mx may act as a promising natural cosmetic ingredient for prevention and treatment of UVB-induced skin damage.

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Section: Discussionsupporting

confidence: 73%

Ginsenoside C‐Mx Isolated from Notoginseng Stem‐leaf Ginsenosides Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts

Liu

Hwang

Park

et al. 2018

Photochem & Photobiology

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“…MMPs produced in UV‐irradiated fibroblasts are modulated through a variety of signaling pathways, including MAPK/AP‐1, NF‐кB and inflammatory cytokines . AP‐1 is a nuclear transcription factor composed of c‐jun and c‐fos, which binds to the promoter region of MMPs genes to induce gene transcription .…”

Section: Discussionmentioning

confidence: 99%

Pterocarpus santalinus L. Regulated Ultraviolet B Irradiation‐induced Procollagen Reduction and Matrix Metalloproteinases Expression Through Activation of TGF‐β/Smad and Inhibition of the MAPK/AP‐1 Pathway in Normal Human Dermal Fibroblasts

Lin

Hwang

Wang

et al. 2017

Photochem & Photobiology

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Ultraviolet light-induced reactive oxygen species (ROS) damage human skin and prematurely cause aging. A growing body of research is focusing on considering plants and plant-derived compounds as antiphotoaging therapeutic material. Pterocarpus santalinus L., as an Indian traditional medicine, possesses antidiabetic, anti-inflammatory and antioxidative effects. Here, we studied the antiphotoaging effects of ethanolic extract of P. santalinus L. heartwood (EPS) on ultraviolet radiation B (UVB)-irradiated normal human dermal fibroblasts (NHDFs). Results showed that EPS significantly inhibited the upregulation of matrix metalloproteinases and IL-6 caused by UVB irradiation, and suppressed UVB-induced phosphorylation of extracellular signal-regulated kinase, Jun N-terminal kinase and p38, as well as the activation of AP-1 transcription factors. Further study indicated that UVB-induced production of MMP-1 and IL-6 could be inhibited by PD 98059 (an ERK inhibitor) and SP600125 (A JNK inhibitor), implied that EPS inhibited UVB-induced MMP-1 and IL-6 secretion by inactivating MAPK signaling pathway. In addition, EPS possessed an excellent antioxidant activity, which could increase cytoprotective antioxidants such as HO-1, NQ-O1 expression by facilitating the nuclear accumulation of Nrf2. Treatment of NHDFs with EPS also recovered UVB-induced procollagen type I reduction by activating TGF-β/Smad pathway. These findings demonstrated that EPS had a potential effect against UVB-induced skin photoaging.

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“…Cadherin and laminin V are the targets of MMP-3-a member of the MMP family of extracellular proteases 24,25 . Furthermore, MMP-3 is a target gene of the transcription factor AP-1, which is located downstream of JNK and p38 [26][27][28][29] . Therefore, we considered that E2 may induce MMP-3 secretion.…”

Section: Estradiol Promotes Mmp-3 Secretion By Mcf-10a Cells and Basmentioning

confidence: 99%

Estradiol/GPER affects the integrity of mammary duct-like structures in vitro

Deng

Miki

Nakanishi

2020

Sci Rep

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High estrogen concentration leads to an inflammatory reaction in the mammary gland tissue in vivo;however, the detailed mechanism underlying its specific effects on the breast duct has not been fully clarified. We used 3D-cultured MCF-10A acini as a breast duct model and demonstrated various deleterious effects of 17-β estradiol (E2), including the destruction of the basement membrane surrounding the acini, abnormal adhesion between cells, and cell death via apoptosis and pyroptosis. Moreover, we clarified the mechanism underlying these phenomena: E2 binds to GPER in MCF-10A cells and stimulates matrix metalloproteinase 3 (MMP-3) and interleukin-1β (IL-1β) secretion via JNK and p38 MAPK signaling pathways. IL-1β activates the IL-1R1 signaling pathway and induces continuous MMP-3 and IL-1β secretion. Collectively, our novel findings reveal an important molecular mechanism underlying the effects of E2 on the integrity of duct-like structures in vitro. Thus, E2 may act as a trigger for ductal carcinoma transition in situ.Estrogens are female hormones secreted mainly by ovaries. They serve diverse functions in the female reproductive organs (e.g., uterus and mammary gland) as well as bones, blood vessels, nerves, and brain 1-4 . Estrogens comprise three types: estrone (E1), 17-β estradiol (E2), and estriol (E3) 5 . E2 binds to estrogen receptors α and β, and the complex formed migrates to DNA of the target gene to activate its transcription 6 . In addition to these classic transcriptional mechanisms, G-protein-coupled receptor 30 (GPER) is an estrogen receptor involved in nongenomic mechanisms 7,8 . GPER expression is tissue-specific, with high expression found in the reproductive system, heart, intestine, ovary, CNS, pancreatic islets, adipose tissue, and neurons. And abnormal GPER expression is associated with depression, hypertension, diabetes, and osteoporosis 9-11 . Also, high GPER expression in breast cancer is associated with increased recurrence 12,13 . Estrogen action via GPER leads to enhanced fibronectin matrix assembly in breast cancer cells 14 . An important biological consequence of GPER activation is the regulation of cell growth and apoptotic cell death 15,16 . In this process, E2 binding to GPER causes G-protein complex dissociation 17,18 , and then the βγ subunit activates the tyrosine kinase Src, which leads to the activation of MAPK pathway 17,18 . GPER activation further activates the downstream signaling molecules such as MAPK and PI3K/ AKT 19,20 .In this study, 3D cultured MCF-10A acini were exposed to E2, which led to the disruption of basement membrane and cell death of some ductal cells. And we further revealed the underlying mechanism in which E2 binding to GPER resulted in cAMP-mediated activation of c-jun N-terminal kinase (JNK) and p38 MAPK signaling pathway, followed by interleukin 1β (IL-1β) and matrix metalloproteinase-3 (MMP-3) expression and secretion. Results Estradiol induces basement membrane disruption in MCF-10A acini.We constructed a 3D model using the immortalized non-transfo...

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Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1 and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts

Cited by 67 publications

References 42 publications

Ginsenoside C‐Mx Isolated from Notoginseng Stem‐leaf Ginsenosides Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts

Ginsenoside C‐Mx Isolated from Notoginseng Stem‐leaf Ginsenosides Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts

Pterocarpus santalinus L. Regulated Ultraviolet B Irradiation‐induced Procollagen Reduction and Matrix Metalloproteinases Expression Through Activation of TGF‐β/Smad and Inhibition of the MAPK/AP‐1 Pathway in Normal Human Dermal Fibroblasts

Estradiol/GPER affects the integrity of mammary duct-like structures in vitro

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