Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Int J Mol Sci. 2018 Mar 29;19(4):1034. doi: 10.3390/ijms19041034.
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.
烧伤后创伤会在损伤初期显著提高组织中血清素的浓度,这促使我们研究其在烧伤创面愈合中的可能作用。因此,我们计划通过烧伤损伤的体外和体内模型来研究血清素在创面愈合中的作用。体外分析的结果表明,血清素可显著减少人成纤维细胞和新生角质形成细胞的凋亡,增加细胞存活率。两种细胞类型的细胞增殖也显著增加。此外,血清素刺激可显著促进细胞迁移,导致人新生儿角质形成细胞和成纤维细胞培养物中的划痕区域变窄。而氟西汀(一种选择性血清素再摄取抑制剂)和酮色林(血清素受体 2A 抑制剂)则逆转了这些效应。烫伤烧伤小鼠模型(20%的全身表面积)表明,内源性血清素可改善对照组的创面愈合过程,而氟西汀和酮色林治疗(干扰内源性血清素刺激)则导致上皮再形成不良、创面更大和α-平滑肌肌动蛋白(α-SMA)计数更高。所有这些迹象都表明处于延长的分化状态,最终表现为创面愈合不良。总之,数据表明内源性血清素通路有助于调节皮肤创面愈合过程。因此,本研究的结果表明,血清素作为一种增强烧伤患者皮肤愈合的潜在治疗候选物的重要性。