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Cell Proliferation and Migration Mechanism of Caffeoylserotonin and Serotonin via Serotonin 2B receptor in Human Keratinocyte HaCaT cells
Hye-Eun Kim1, Hyejoung Cho1, Atsushi Ishihara1, Byungkuk Kim1, Okjoon Kim1,*
1Department of Oral Pathology, Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Kor,
2Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan
Abstract
Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP-1/MMP9 pathway while additional Akt/NF-リB/MMP9 pathway was involved in the cell migration effect of CaS. These results suggest that CaS can enhance keratinocyte proliferation and migration. It might have potential as a reagent beneficial for wound closing and cell regeneration.
Abstract, Accepted Manuscript(in press) [Submitted on October 31, 2017, Accepted on January 5, 2018]
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