The Role of Serotonin during Skin Healing in Post-Thermal Injury.

Alia Sadiq,Marc Jeschke,Ahmed Shah,Saeid Amini-Nik,Sheeba Murad,Cassandra Belo,Muhammad Qasim Hayat

doi:10.3390/ijms19041034

Abstract

Post-burn trauma significantly raises tissue serotonin concentration at the initial stages of injury, which leads us to investigate its possible role in post burn wound healing. Therefore, we planned this study to examine the role of serotonin in wound healing through in vitro and in vivo models of burn injuries. Results from in vitro analysis revealed that serotonin decreased apoptosis and increased cell survival significantly in human fibroblasts and neonatal keratinocytes. Cellular proliferation also increased significantly in both cell types. Moreover, serotonin stimulation significantly accelerated the cell migration, resulting in narrowing of the scratch zone in human neonatal keratinocytes and fibroblasts cultures. Whereas, fluoxetine (a selective serotonin reuptake inhibitor) and ketanserin (serotonin receptor 2A inhibitor) reversed these effects. Scald burn mice model (20% total body surface area) showed that endogenous serotonin improved wound healing process in control group, whereas fluoxetine and ketanserin treatments (disruptors of endogenous serotonin stimulation), resulted in poor reepithelization, bigger wound size and high alpha smooth muscle actin (α-SMA) count. All of these signs refer a prolonged differentiation state, which ultimately exhibits poor wound healing outcomes. Collectively, data showed that the endogenous serotonin pathway contributes to regulating the skin wound healing process. Hence, the results of this study signify the importance of serotonin as a potential therapeutic candidate for enhancing skin healing in burn patients.

Highlights

Severe burn wound injuries have become a global public health challenge, which presents a significant financial, psychological and emotional burden on patients and physicians [1,2]
The effect of serotonin signaling on cell viability of human fibroblasts and neonatal keratinocytes was investigated (Figure 1)
Results revealed that serotonin treatment enhanced cell survival significantly (Relative Luminescent Unit, RLU = 41.51 × 103 ± 1.45) in human fibroblasts (Figure 1A) and keratinocytes (RLU = 98.9 × 103 ± 4.6) (Figure 1E), as compared to the respective control group, whereas cell viability reduced significantly upon interrupted serotonin signaling by the addition of

Summary

Introduction

Severe burn wound injuries have become a global public health challenge, which presents a significant financial, psychological and emotional burden on patients and physicians [1,2]. World Health Organization (WHO) estimates that fire-related burn injuries alone result in more than 300,000 deaths and loss of 10 million Disability Adjusted Life Years (DALYs) each year [3]. Developing countries share most of the global burden of burn injuries but the mortality rate associated with burn injuries in developed countries such as United States (US) is still significant (5.3%) [4]. High mortality in burn patients is mainly due to loss of skin cover resulting in increased metabolic demand, fluid loss and significant risk of infections [5,6,7]. Current treatments include grafting or reconstruction and skin engineering [8,9,10]; the ultimate therapeutic goal is to enhance and accelerate the wound healing process by activating respective signaling pathways of healing

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Results

Discussion

Conclusion