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Esculetin promotes type I procollagen expression in human dermal fibroblasts through MAPK and PI3K/Akt pathways

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Abstract

Type I collagen is the major constituent of the skin and the reduction of dermal type I collagen content is closely associated with the intrinsic skin aging. We here found that esculetin, 6,7-dihydroxycoumarin, strongly induces type I procollagen expression in human dermal fibroblasts. Esculetin not only increased protein levels of type I procollagen but also increased mRNA levels of COL1A1 but not COL1A2. Esculetin activated the MAPKs (ERK1/2, p38, JNK) and PI3K/Akt pathways, through which it promoted the type I procollagen expression. We also demonstrated that the binding motifs for transcription factor Sp1 occur with the highest frequency in the COL1A1 promoter and that esculetin increases the Sp1 expression through the MAPK and PI3K/Akt pathways. These results suggest that esculetin promotes type I procollagen expression through the MAPK and PI3K/Akt pathways and that Sp1 might be involved in the esculetin-induced type I procollagen expression via activation of the COL1A1 transcription.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0007188), a grant from the National R&D Program for Cancer Control, Ministry for Health and welfare, Republic of Korea (1020420), and the Nutraceutical Bio Brain Korea 21 Project and Well-being Bioproducts Regional Innovation Center Project of Kangwon National University in 2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Jung Hae Park, So Ra Kim, Hyun Ju An & Jeong A. Han

  2. Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Woo Jin Kim

  3. Department of Biohealth Technology, College of Biomedical Science, Kangwon National University, Chuncheon, 200-701, South Korea

    Myeon Choe

  4. Institute of Medical Sciences, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Jeong A. Han

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  1. Jung Hae Park
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Correspondence to Jeong A. Han.

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Park, J.H., Kim, S.R., An, H.J. et al. Esculetin promotes type I procollagen expression in human dermal fibroblasts through MAPK and PI3K/Akt pathways. Mol Cell Biochem 368, 61–67 (2012). https://doi.org/10.1007/s11010-012-1342-7

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  • DOI: https://doi.org/10.1007/s11010-012-1342-7

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