5-HT1A Receptor Function Makes Wound Healing a Happier Process

Skin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydr...

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Main Authors: Alia Sadiq, Isabella Menchetti, Ahmed Shah, Marc G. Jeschke, Cassandra Belo, Wendolyn Carlos-Alcalde, Muhammad Qasim Hayat, Saeid Amini-Nik
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2018.01406/full
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author Alia Sadiq
Alia Sadiq
Alia Sadiq
Isabella Menchetti
Ahmed Shah
Ahmed Shah
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Cassandra Belo
Wendolyn Carlos-Alcalde
Wendolyn Carlos-Alcalde
Muhammad Qasim Hayat
Saeid Amini-Nik
Saeid Amini-Nik
Saeid Amini-Nik
Saeid Amini-Nik
author_facet Alia Sadiq
Alia Sadiq
Alia Sadiq
Isabella Menchetti
Ahmed Shah
Ahmed Shah
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Cassandra Belo
Wendolyn Carlos-Alcalde
Wendolyn Carlos-Alcalde
Muhammad Qasim Hayat
Saeid Amini-Nik
Saeid Amini-Nik
Saeid Amini-Nik
Saeid Amini-Nik
author_sort Alia Sadiq
collection DOAJ
description Skin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis revealed 5-Ht1a receptor knockout mice showed impaired skin healing, accompanied by a greater number of F4/80 macrophages, which prolongs the inflammatory phase of wound healing. To further unravel this phenomenon, we employed the 5-HT1A receptor agonist [(R)-(+)-8-Hydroxy-DPAT hydrobromide] as a topical cream treatment in an excisional punch biopsy model. The 5-HT1A receptor agonist treated group showed a smaller wound area, scar size, and improved neovascularization, which contributed to improve healing outcomes as compared to the control. Collectively, these findings revealed that serotonin and 5-HT1A receptor play an important role during the healing process. These findings may open new lines of investigation for the potential treatment alternatives to improve skin healing with minimal scarring.
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spelling doaj.art-a6c951569feb490480328f2e4671e4402022-12-22T01:11:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-12-01910.3389/fphar.2018.014064108065-HT1A Receptor Function Makes Wound Healing a Happier ProcessAlia Sadiq0Alia Sadiq1Alia Sadiq2Isabella Menchetti3Ahmed Shah4Ahmed Shah5Marc G. Jeschke6Marc G. Jeschke7Marc G. Jeschke8Marc G. Jeschke9Marc G. Jeschke10Cassandra Belo11Wendolyn Carlos-Alcalde12Wendolyn Carlos-Alcalde13Muhammad Qasim Hayat14Saeid Amini-Nik15Saeid Amini-Nik16Saeid Amini-Nik17Saeid Amini-Nik18Sunnybrook Research Institute, Toronto, ON, CanadaAtta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Islamabad, PakistanDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaDivision of Plastic Surgery, Department of Surgery, University of Toronto, Toronto, ON, CanadaDepartment of Immunology, University of Toronto, Toronto, ON, CanadaRoss Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaAtta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology, Islamabad, PakistanSunnybrook Research Institute, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaDivision of Plastic Surgery, Department of Surgery, University of Toronto, Toronto, ON, CanadaLaboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaSkin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis revealed 5-Ht1a receptor knockout mice showed impaired skin healing, accompanied by a greater number of F4/80 macrophages, which prolongs the inflammatory phase of wound healing. To further unravel this phenomenon, we employed the 5-HT1A receptor agonist [(R)-(+)-8-Hydroxy-DPAT hydrobromide] as a topical cream treatment in an excisional punch biopsy model. The 5-HT1A receptor agonist treated group showed a smaller wound area, scar size, and improved neovascularization, which contributed to improve healing outcomes as compared to the control. Collectively, these findings revealed that serotonin and 5-HT1A receptor play an important role during the healing process. These findings may open new lines of investigation for the potential treatment alternatives to improve skin healing with minimal scarring.https://www.frontiersin.org/article/10.3389/fphar.2018.01406/fullserotonin5-HT1A receptorwound healing5-Ht1a receptor knockout mice modelskin regeneration
spellingShingle Alia Sadiq
Alia Sadiq
Alia Sadiq
Isabella Menchetti
Ahmed Shah
Ahmed Shah
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Marc G. Jeschke
Cassandra Belo
Wendolyn Carlos-Alcalde
Wendolyn Carlos-Alcalde
Muhammad Qasim Hayat
Saeid Amini-Nik
Saeid Amini-Nik
Saeid Amini-Nik
Saeid Amini-Nik
5-HT1A Receptor Function Makes Wound Healing a Happier Process
Frontiers in Pharmacology
serotonin
5-HT1A receptor
wound healing
5-Ht1a receptor knockout mice model
skin regeneration
title 5-HT1A Receptor Function Makes Wound Healing a Happier Process
title_full 5-HT1A Receptor Function Makes Wound Healing a Happier Process
title_fullStr 5-HT1A Receptor Function Makes Wound Healing a Happier Process
title_full_unstemmed 5-HT1A Receptor Function Makes Wound Healing a Happier Process
title_short 5-HT1A Receptor Function Makes Wound Healing a Happier Process
title_sort 5 ht1a receptor function makes wound healing a happier process
topic serotonin
5-HT1A receptor
wound healing
5-Ht1a receptor knockout mice model
skin regeneration
url https://www.frontiersin.org/article/10.3389/fphar.2018.01406/full
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