Abstract
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.
Highlights
The skin healing of full-thickness open wounds depends on a series of major cellular processes: epithelialization, cellular proliferation, migration, formation and contraction of granulation tissue
Ubiquitous knock out of this receptor may not reveal all the cell types that are predominantly affected by this receptor, our in vitro data supports the notion that the 5-HT1A receptor influences the course of skin healing partly through fibroblast migration, an essential component of skin healing
This study advances our understanding about the role of serotonin through its 5-HT1A receptor in cutaneous wound healing
Summary
The skin healing of full-thickness open wounds depends on a series of major cellular processes: epithelialization, cellular proliferation, migration, formation and contraction of granulation tissue. Inflammatory cells (such as macrophages) release growth factors to enhance fibroblast and epithelial cell migration into the wound area (Amini-Nik et al, 2011, 2014; Bielefeld et al, 2011). The wound healing process ends with scar formation (permanent deposition of connective tissue characterized by the presence of fibroblasts, extracellular matrix components, among which collagen is the most important component (Arno et al, 2014a; Amini-Nik et al, 2017; Amini-Nik, 2018). Excessive extracellular matrix deposition may continue for several years; such processes are exhibited in hypertrophic scars and fibrotic lesions (Gabbiani, 2003)
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