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Association between sphingosine-1-phosphate-induced signal transduction via mitogen-activated protein kinase pathways and keloid formation

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Abstract

We conducted this experimental study to analyze the relationship between sphingosine-1-phosphate (S1P)-induced mitogen-activated protein (MAP) kinase pathways and keloid formation. We collected samples of the normal tissue and the keloid tissue from 10 normal healthy individuals and 12 patients with keloid scars, respectively. Then, we compared the level of sphingosine-1-phosphate receptor (S1PR1/S1PR2) mRNA/protein expression between the normal tissue and the keloid tissue. Moreover, we also compared the level of S1PR protein expression, that of S1P-induced COL1A1 (collagen Type I, α-1 chain) expression, that of S1P-induced JNK/ERK phosphorylation, that of S1P-induced COL1A1 expression following the treatment with 30 μM PD98059 (ERK inhibitor) or 30 μM SP600125 (JNK inhibitor) and that of S1P-induced COL1A1 expression following the treatment with W146 (S1PR1 inhibitor) or JTE013 (S1PR2 inhibitor) between the normal fibroblasts and the keloid fibroblasts. We found that the level of S1PR1/S1PR2 mRNA/protein expression was significantly higher in the keloid tissue as compared with the normal tissue. Our results also showed that the level of S1P-induced COL1A1 expression and that of S1P-induced JNK/ERK phosphorylation were significantly higher in the keloid fibroblasts as compared with the normal ones (P < 0.05). Furthermore, there were significant decreases in the level of S1P-induced COL1A1 expression when the keloid fibroblasts were treated with 30 μM SP600125 or 30 μM PD98059 and that of S1P-induced COL1A1 expression when the treated with 100 nM W146 or 100 nM JTE013 (P < 0.05). Our results indicate that S1P-induced signal transduction is associated with increased collagen synthesis via S1PR-mediated signaling pathways in the keloid tissue.

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Acknowledgments

This work was supported by the Korean Research Foundation grant funded by the Korean Government (KRF-2010–0006841).

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Non-applicable.

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Authors and Affiliations

  1. Research Institute of Medical Science, Konkuk University School of Medicine, 82 Gugwon-daero, Chungju, 27376, Korea

    Seung Hyo Jung & Bokyung Kim

  2. Department of Plastic and Reconstructive Surgery, Konkuk University School of Medicine, Konkuk University Chungju Hospital, 82 Gugwon-daero, Chungju, 27376, Korea

    Yu Kwan Song, Dong In Jo & Soon Heum Kim

  3. Department of Medicine, Konkuk University School of Medicine, Konkuk University Chungju Hospital, 82 Gugwon-daero, Chungju, 27376, Korea

    Hong Chung

  4. Department of Eco-Biological Science, College of Science and Technology, Woosuk University, Jincheon-eup, Jincheon-gun, Chungbuk, 27841, Korea

    Hyun Myung Ko

  5. Department of Pharmacy, College of Pharmacy, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul, 06974, Korea

    Sung Hoon Lee

  6. Gyeongbuk Institute for Bio Industry, Gyeongbuk, Korea

    Dong Hee Lee

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  1. Seung Hyo Jung
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Correspondence to Soon Heum Kim.

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The authors declared that they have no conflict of interest.

Informed consent

Informed consent of the patients was waived due to retrospective nature of the current study. But their normal controls submitted a written informed consent.

Ethical standards

The current study was conducted in accordance with the Declaration of Helsinki. The experimental protocol was approved by the Institutional Review Board (IRB) of our medical institution (IRB approval # CR316049). All the experimental procedures were performed during September of 2016.

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Jung, S.H., Song, Y.K., Chung, H. et al. Association between sphingosine-1-phosphate-induced signal transduction via mitogen-activated protein kinase pathways and keloid formation. Arch Dermatol Res 311, 711–719 (2019). https://doi.org/10.1007/s00403-019-01961-6

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  • DOI: https://doi.org/10.1007/s00403-019-01961-6

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