UV-induced DNA methyltransferase 1 promotes hypermethylation of tissue inhibitor of metalloproteinase 2 in the human skin

Kim, Ha Young; Lee, Dong Hun; Shin, Mi Hee; Shin, Hyun Soo; Kim, Min Kyoung; Chung, Jin Ho

doi:10.1016/j.jdermsci.2018.03.009

Cited by 16 publications

(13 citation statements)

References 41 publications

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“…Previous reports had shown that ultraviolet exposure increases the DNMTs expression, as they are also elevated in photodamaged skin [16]. Thus, the augmented expression may be related to a damaged microenvironmental skin with an associated DNA hypermethylation status [16]. On the other hand, DNMT3b expression in melasma was similar to unaffected skin, but it was reduced after eight weeks of treatment in all three groups compared to its basal values.…”

Section: Discussionmentioning

confidence: 64%

“…The greater expression and activity of DNMT1 found in melasma lesions than in unaffected skin is probably related to solar exposure. Previous reports had shown that ultraviolet exposure increases the DNMTs expression, as they are also elevated in photodamaged skin [16]. Thus, the augmented expression may be related to a damaged microenvironmental skin with an associated DNA hypermethylation status [16].…”

Section: Discussionmentioning

confidence: 99%

“…Niacinamide and retinoic acid may be inhibiting them by downregulating the presence of reactive oxygen species (ROS) which are DNMTs activators [26, 27]; retinoic acid in addition may be activating miRNAs, such as miR-152 that decreases DNMTs [28]. The sunscreen use may be blocking the enzyme methylation genes induced by solar ultraviolet radiation conditioning its inhibition [16, 24]. Thus, the melasma improvement, accompanied by the reduction of both enzymes on different locations, implies that treatment acts on diverse layers of the epidermis.…”

Section: Discussionmentioning

confidence: 99%

“…In relation to photoprotection, it is well recognized that sunscreen reduces the severity of melasma [15]. This may reduce the genotoxic action of solar ultraviolet radiation on skin cells that prevents DNMTs activity and further genome methylation [16]. Therefore, in this study we sought to quantify the expression and activity of DNMTs that affect the basal conditions of DNA methylation in skin with malar melasma, and their modification following its treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo.…”

Section: Introductionmentioning

confidence: 99%

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DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo

Campuzano-Garcia

Torres-Álvarez

Hernández-Blanco

et al. 2019

BioMed Research International

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Background. Malar melasma has a chronic and recurrent character that may be related to epigenetic changes. Objective. To recognize the expression and DNA methylation of DNA methyltransferases (DNMTs) in malar melasma and perilesional skin, as well as the changes in DNMTs after their treatment with sunscreen in combination with 4% niacinamide, 0.05% retinoic acid, or placebo. Methods. Thirty female patients were clinically evaluated for the expression of DNMT1 and DNMT3b using real-time PCR and immunofluorescence. These initial results were compared to results after eight weeks of treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo. Results. The relative expression of DNMT1 was significantly elevated in melasma compared with unaffected skin in all subjects, indicating DNA hypermethylation. After treatment, it was decreased in all groups: niacinamide (7 versus 1; p<0.01), retinoic acid (7 versus 2; p<0.05), and placebo (7 versus 3; p<0.05), which correlates with clinical improvement. DNMT3b was not overexpressed in lesional skin but reduced in all groups. Conclusions. We found DNA hypermethylation in melasma lesions. Environmental factors such as solar radiation may induce cellular changes that trigger hyperpigmentation through the activation of pathways regulated by epigenetic modifications. However, limiting or decreasing DNA methylation through sunscreen, niacinamide, and retinoic acid treatments that provide photoprotection and genetic transcription can counteract this.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo

Campuzano-Garcia

Torres-Álvarez

Hernández-Blanco

et al. 2019

BioMed Research International

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“…Intrinsic aging and photoaging share several molecular changes, such as altered signal transduction pathways that promote the expression of MMPs and decrease the synthesis of procollagen [11]. Recent studies suggest that skin aging-related gene expression is regulated via epigenetic mechanisms, such as chromatin modification and DNA methylation [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Increased Histone Acetylation and Decreased Expression of Specific Histone Deacetylases in Ultraviolet-Irradiated and Intrinsically Aged Human Skin In Vivo

Lee

Shin

Kim

et al. 2021

IJMS

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Histone deacetylases (HDACs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins and play a crucial role in epigenetic regulation. Previously, we showed that histone acetylation is implicated in ultraviolet (UV)-induced inflammation and matrix impairment. To elucidate the histone acetylation status and specific HDACs involved in skin aging, we examined the changes in histone acetylation, global HDAC activity, and the expression of HDACs and sirtuins (SIRTs) in intrinsically aged and photoaged human skin as well as in UV-irradiated human skin in vivo. Following acute UV irradiation, the acetylated histone H3 (AcH3) level was increased, but HDAC activity and the expression levels of HDAC4, HDAC11, and SIRT4 were significantly decreased. In intrinsically aged skin, AcH3 levels were increased, but HDAC activity and the expression levels of HDAC4, HDAC5, HDAC10, HDAC11, SIRT6, and SIRT7 were significantly decreased. However, histone acetylation and HDAC expression in photoaged skin were not significantly different from those in intrinsically aged skin. Collectively, HDAC4 and HDAC11 were decreased in both UV-irradiated and intrinsically aged skin, suggesting that they may play a universal role in increased histone acetylation associated with skin aging.

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Long noncoding RNA MEG3 silencing protects against hypoxia‐induced pheochromocytoma‐12 cell injury through inhibition of TIMP2 promoter methylation

Zheng

Lei

Lin

et al. 2019

Journal Cellular Physiology

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Hypoxia is a common pathological process caused by insufficient oxygen. Long noncoding RNAs (lncRNAs) have been proven to participate in this pathology. Hypoxia is reported to significantly reduce the secretion of tissue inhibitor of metalloproteinase 2 (TIMP2) and TIMP2 induces pheochromocytoma-12 (PC12) cell cycle arrest. Thus, our study aimed to explore the mechanism by which lncRNA maternally expressed gene 3 (MEG3) was implicated in hypoxia-induced PC12 cell injury through TIMP2 promoter methylation. To elucidate the potential biological significance of MEG3 and the regulatory mechanism between MEG3 and TIMP2, a hypoxia-induced PC12 cell injury model was generated. The hypoxia-exposed cells were subjected to a series of overexpression plasmids and short hairpin RNAs, followed by the measurement of levels of MEG3, TIMP2, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), Bcl-2-associated X protein, B-cell lymphoma-2, and caspase-3, as well as the changes in MMP, cell proliferation, apoptosis, and cell cycle progression. On the basis of the findings, MEG3 was upregulated in hypoxia-injured PC12 cells. MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression. Moreover, PC12 cells following MEG3 silencing and TIMP2 overexpression exhibited significantly decreased levels of LDH, MDA, and ROS along with cell apoptosis, yet increased SOD and MMP levels, as well as cell cycle entry to the S phase and cell proliferation. In conclusion, MEG3 silencing suppresses hypoxiainduced PC12 cell injury by inhibiting TIMP2 promoter methylation. This study may provide novel therapeutic targets for hypoxia-induced injury. K E Y W O R D S hypoxic injury, long noncoding RNA, MEG3, pheochromocytoma-12 cell, promoter methylation,TIMP2

show abstract

UV-induced DNA methyltransferase 1 promotes hypermethylation of tissue inhibitor of metalloproteinase 2 in the human skin

Cited by 16 publications

References 41 publications

DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo

DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo

Increased Histone Acetylation and Decreased Expression of Specific Histone Deacetylases in Ultraviolet-Irradiated and Intrinsically Aged Human Skin In Vivo

Long noncoding RNA MEG3 silencing protects against hypoxia‐induced pheochromocytoma‐12 cell injury through inhibition of TIMP2 promoter methylation

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