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Inhibition of EGR-1-dependent MMP1 transcription by ethanol extract of Ageratum houstonianum in HaCaT keratinocytes

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Abstract

Matrix metalloproteinase 1 (MMP-1) initiates the breakdown of matrix networks by cleaving fibrillar collagen during the pathophysiological progression of skin aging. Ageratum houstonianum ethanol extract (AHE) has been used as a traditional herbal medicine to treat external wounds and skin diseases. However, the mechanism of action underlying A. houstonianum-mediated modulation of skin aging has not been investigated. In this study, we evaluated the effect of AHE on MMP-1 expression in HaCaT keratinocytes. Gene expression was analyzed by Reverse transcription-PCR (RT-PCR), Quantitative real-time PCR (Q-PCR), gene promoter-reporter assay, and immunoblotting. We found that AHE abrogated TNFα-induced MMP1 expression at the transcriptional level via the suppression of ERK1/2 mitogen-activated protein kinase (MAPK)-mediated Early Growth Response 1 (EGR1) expression. We also demonstrated that β-caryophyllene, a cannabinoid receptor 2 (CB2) agonist, is a functional component of the AHE that inhibits TNFα-induced EGR-1 and MMP1 expression. AHE exerts inhibitory activity on TNFα-induced MMP1 expression at the transcription level through EGR-1 downregulation in keratinocytes. β-Caryophyllene is a bioactive ingredient of AHE that is responsible for the inhibition of TNFα-induced EGR1 expression. β-Caryophyllene can be used as a potential agent to prevent inflammation-induced skin aging.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

AHE:

Ageratum houstonianum ethanol extract

EGR1:

Early Growth Response 1

JNK:

c-Jun NH2-terminal kinase

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

IL:

interleukin

Q-PCR:

quantitative real-time PCR

MMP-1:

matrix metalloproteinase 1

MAPK:

mitogen-activated protein kinase

RT-PCR:

reverse transcription-PCR

TNFα:

tumor necrosis factor α

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Acknowledgements

The paper was supported by the KU Research Professor Program of Konkuk University.

Funding

This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2020R1A2C1005845).

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Authors and Affiliations

  1. Department of Biological Sciences, Konkuk University, Seoul, 05029, Republic of Korea

    Soon Young Shin & Young Han Lee

  2. Cancer and Metabolism Institute, Konkuk University, Seoul, 05029, Republic of Korea

    Soon Young Shin & Young Han Lee

  3. Department of Applied Chemistry, Dongduk Women’s University, Seoul, 02748, Republic of Korea

    Dongsoo Koh

  4. Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul, 05029, Republic of Korea

    Yoongho Lim

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  1. Soon Young Shin
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Soon Young Shin, Dongsoo Koh and Yoongho Lim. The first draft of the manuscript was written by Soon Young Shin, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Young Han Lee.

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Shin, S.Y., Koh, D., Lim, Y. et al. Inhibition of EGR-1-dependent MMP1 transcription by ethanol extract of Ageratum houstonianum in HaCaT keratinocytes. Mol Biol Rep 48, 1–11 (2021). https://doi.org/10.1007/s11033-020-06091-1

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