Cited by 101Skin Protection and AgingGenomics, phytochemicals, and oxidative stressmelanin and skin pigmentation

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Activation of Nrf2 Reduces UVA-Mediated MMP-1 Upregulation via MAPK/AP-1 Signaling Cascades: The Photoprotective Effects of Sulforaphane and Hispidulin

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Chaiprasongsuk, Anyamanee, Lohakul, Jinaphat, Soontrapa, Kitipong, Sampattavanich, Somponnat, Akarasereenont, Pravit, Panich, Uraiwan·2017·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1124/jpet.116.238048PMC PMC5325073

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Abstract

UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates.

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1 retracted

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Method
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Authors: Chaiprasongsuk, A., Lohakul, J., Soontrapa, K., Sampattavanich, S., Akarasereenont, P., & Panich, U.
Affiliations: Siriraj Hospital (TH)
Corresponding author: Panich, Uraiwan
ORCID: Chaiprasongsuk, Anyamanee
Soontrapa, Kitipong
Sampattavanich, Somponnat
Akarasereenont, Pravit
Panich, Uraiwan
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 2017-03
Volume: 360
Issue: 3
Pages: 388-398
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1124/jpet.116.238048
PMC: PMC5325073
OpenAlex: W2563575197
Cited by: 101
References: 54
Citations by year: 2026: 11 · 2025: 10 · 2024: 13 · 2023: 7 · 2022: 12 · 2021: 14 · 2020: 15 · 2019: 15 · 2018: 4
FWCI: 7.57
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc/4.0/ (vor, 2863 d)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Mahidol University
Thailand Research Fund (RSA5980066)
National Research Council of Thailand
Faculty of Medicine Siriraj Hospital, Mahidol University
Topics: Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Keywords: Nrf2, UVA irradiation, MMP-1, MAPK signaling, AP-1, hispidulin, sulforaphane, photoaging, skin aging, collagen degradation, keratinocytes, c-Jun, c-fos, oxidative stress, photoprotection
MeSH terms: Animals, Cell Line, Collagen, Enzyme Activation, Humans, Skin, Sulfoxides, Ultraviolet Rays, Skin Aging, Keratinocytes, Up-Regulation, Antimutagenic Agents, Isothiocyanates, Oxidative Stress, Transcription Factor AP-1, Aging, Premature, Matrix Metalloproteinase 1, MAP Kinase Signaling System, Flavones, NF-E2-Related Factor 2, Mice

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Activation of Nrf2 Reduces UVA-Mediated MMP-1 Upregulation via MAPK/AP-1 Signaling Cascades: The Photoprotective Effects of Sulforaphane and Hispidulin

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