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Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation

1
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, Japan
2
Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, VA 23298-0011, USA
3
Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan
4
Department of Molecular Pathology, Osaka University, Suita 565-0871, Japan
5
Division of Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
6
Department of Surgery, University at Buffalo Jacob School of Medicine and Biomedical Sciences, the State University of New York, Buffalo, NY 14203, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3381; https://doi.org/10.3390/ijms20143381
Received: 11 June 2019 / Revised: 8 July 2019 / Accepted: 8 July 2019 / Published: 10 July 2019
(This article belongs to the Special Issue Wound Repair and Regeneration: Mechanisms, Signaling)
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Abstract

Wound healing starts with the recruitment of inflammatory cells that secrete wound-related factors. This step is followed by fibroblast activation and tissue construction. Sphingosine-1-phosphate (S1P) is a lipid mediator that promotes angiogenesis, cell proliferation, and attracts immune cells. We investigated the roles of S1P in skin wound healing by altering the expression of its biogenic enzyme, sphingosine kinase-1 (SphK1). The murine excisional wound splinting model was used. Sphingosine kinase-1 (SphK1) was highly expressed in murine wounds and that SphK1−/− mice exhibit delayed wound closure along with less angiogenesis and inflammatory cell recruitment. Nanoparticle-mediated topical SphK1 overexpression accelerated wound closure, which associated with increased angiogenesis, inflammatory cell recruitment, and various wound-related factors. The SphK1 overexpression also led to less scarring, and the interaction between transforming growth factor (TGF)-β1 and S1P receptor-2 (S1PR2) signaling is likely to play a key role. In summary, SphK1 play important roles to strengthen immunity, and contributes early wound healing with suppressed scarring. S1P can be a novel therapeutic molecule with anti-scarring effect in surgical, trauma, and chronic wound management. View Full-Text
Keywords: sphingosine-1-phosphate; sphingosine kinase-1; sphingosine1-phosphate receptor-2; skin wound healing sphingosine-1-phosphate; sphingosine kinase-1; sphingosine1-phosphate receptor-2; skin wound healing
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Aoki, M.; Aoki, H.; Mukhopadhyay, P.; Tsuge, T.; Yamamoto, H.; Matsumoto, N.M.; Toyohara, E.; Okubo, Y.; Ogawa, R.; Takabe, K. Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation. Int. J. Mol. Sci. 2019, 20, 3381.

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