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Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway
The 5-HT2A serotonin receptor (HTR2A) has been reported to be involved in the serotonin- or serotonin receptor 2A agonist-induced melanogenesis in human melanoma cells. However, the molecular mechanisms underlying HTR2A in regulating melanogenesis remain poorly understood. In this research, cultured...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245606/ https://www.ncbi.nlm.nih.gov/pubmed/35682806 http://dx.doi.org/10.3390/ijms23116111 |
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author | Yue, Yunyun Zhong, Min An, Xiaohong Feng, Qingyuan Lai, Yifan Yu, Meng Zhang, Xiaofeng Liao, Zixian Chen, Minghan Dong, Jing Zhong, Hui Shang, Jing |
author_facet | Yue, Yunyun Zhong, Min An, Xiaohong Feng, Qingyuan Lai, Yifan Yu, Meng Zhang, Xiaofeng Liao, Zixian Chen, Minghan Dong, Jing Zhong, Hui Shang, Jing |
author_sort | Yue, Yunyun |
collection | PubMed |
description | The 5-HT2A serotonin receptor (HTR2A) has been reported to be involved in the serotonin- or serotonin receptor 2A agonist-induced melanogenesis in human melanoma cells. However, the molecular mechanisms underlying HTR2A in regulating melanogenesis remain poorly understood. In this research, cultured mouse melanoma cell line B16F10, human skin, and zebrafish embryos were used to elucidate the downstream signaling of HTR2A in regulating melanogenesis and to verify the potential application of HTR2A in the treatment of pigment-associated cutaneous diseases. We demonstrated that HTR2A antagonists (AT1015 and ketanserin) attenuated the melanogenesis induction of serotonin in both mouse melanoma cells and zebrafish embryos. The agonists of HTR2A (DOI and TCB-2) increased melanin synthesis and transfer in B16F10 cells, human skin tissue, and zebrafish embryos. Furthermore, the HTR2A agonists increased the expression of proteins related to melanosome organization and melanocyte dendrites to facilitate the melanocyte migration and melanosome transport. HTR2A antagonists and genetic knockout of zebrafish htr2aa (the homologue of mammalian HTR2A gene) were also used to clarify that HTR2A mediates serotonin and DOI in regulating melanogenesis. Finally, through small scale screening of the candidate downstream pathway, we demonstrated that HTR2A mediates the melanogenesis induction of its ligands by activating the PKA/CREB signaling pathway. In this research, we further confirmed that HTR2A is a crucial protein to mediate melanocyte function. Meanwhile, this research supports that HTR2A could be designed as a drug target for the development of chemicals to treat cutaneous diseases with melanocytes or melanogenesis abnormality. |
format | Online Article Text |
id | pubmed-9245606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92456062022-07-01 Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway Yue, Yunyun Zhong, Min An, Xiaohong Feng, Qingyuan Lai, Yifan Yu, Meng Zhang, Xiaofeng Liao, Zixian Chen, Minghan Dong, Jing Zhong, Hui Shang, Jing Int J Mol Sci Article The 5-HT2A serotonin receptor (HTR2A) has been reported to be involved in the serotonin- or serotonin receptor 2A agonist-induced melanogenesis in human melanoma cells. However, the molecular mechanisms underlying HTR2A in regulating melanogenesis remain poorly understood. In this research, cultured mouse melanoma cell line B16F10, human skin, and zebrafish embryos were used to elucidate the downstream signaling of HTR2A in regulating melanogenesis and to verify the potential application of HTR2A in the treatment of pigment-associated cutaneous diseases. We demonstrated that HTR2A antagonists (AT1015 and ketanserin) attenuated the melanogenesis induction of serotonin in both mouse melanoma cells and zebrafish embryos. The agonists of HTR2A (DOI and TCB-2) increased melanin synthesis and transfer in B16F10 cells, human skin tissue, and zebrafish embryos. Furthermore, the HTR2A agonists increased the expression of proteins related to melanosome organization and melanocyte dendrites to facilitate the melanocyte migration and melanosome transport. HTR2A antagonists and genetic knockout of zebrafish htr2aa (the homologue of mammalian HTR2A gene) were also used to clarify that HTR2A mediates serotonin and DOI in regulating melanogenesis. Finally, through small scale screening of the candidate downstream pathway, we demonstrated that HTR2A mediates the melanogenesis induction of its ligands by activating the PKA/CREB signaling pathway. In this research, we further confirmed that HTR2A is a crucial protein to mediate melanocyte function. Meanwhile, this research supports that HTR2A could be designed as a drug target for the development of chemicals to treat cutaneous diseases with melanocytes or melanogenesis abnormality. MDPI 2022-05-30 /pmc/articles/PMC9245606/ /pubmed/35682806 http://dx.doi.org/10.3390/ijms23116111 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yue, Yunyun Zhong, Min An, Xiaohong Feng, Qingyuan Lai, Yifan Yu, Meng Zhang, Xiaofeng Liao, Zixian Chen, Minghan Dong, Jing Zhong, Hui Shang, Jing Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway |
title | Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway |
title_full | Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway |
title_fullStr | Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway |
title_full_unstemmed | Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway |
title_short | Serotonin (5-HT) 2A Receptor Involvement in Melanin Synthesis and Transfer via Activating the PKA/CREB Signaling Pathway |
title_sort | serotonin (5-ht) 2a receptor involvement in melanin synthesis and transfer via activating the pka/creb signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245606/ https://www.ncbi.nlm.nih.gov/pubmed/35682806 http://dx.doi.org/10.3390/ijms23116111 |
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