Improved cutaneous wound healing after intraperitoneal injection of alpha‐melanocyte‐stimulating hormone

Abstract

Skin wound healing is a complex process involving many types of cells and molecules and often results in scar tissue formation in adult mammals. However, scarless healing occurs in foetal skin and minimal scars may occur after cutaneous healing in the adult with reduced inflammation. Alpha-melanocyte-stimulating hormone (α-MSH) is widely distributed within the central nervous system and in other body regions, such as the skin, and has strong anti-inflammatory activity. The aim in the present experiments was to learn whether intraperitoneal (i.p) injection of α-MSH just before skin wounds antagonize inflammation and improves skin wound healing in adult mice. C57BL/6 young adult mice received an i.p. injection of 1 mg/kg of α-MSH and, 30 min later, two circular through-and-through holes (6.5 mm diameter) were made in their dorsal skin under anaesthesia. Control mice were wounded after vehicle injection. The wound healing process was analysed macroscopically and microscopically at 3, 7, 40 and 60 days. Skin samples were fixed in formalin, embedded in paraffin, sectioned at 5 μm, stained with H&E or toluidine blue for cell analysis or Gomori's trichrome for extracellular matrix (ECM) analysis. Other samples were fixed in DMSO+methanol, embedded in paraplast and incubated with anti-CD45, antismooth muscle actin, anticollagen-I and anticollagen-III for immunofluorescence analysis. Alpha-MSH significantly reduced the number of leucocytes, mast cells and fibroblasts at 3 and 7 days after injury. On days 40 and 60, α-MSH reduced scar area and improved the organization of the collagen fibres indicating that it may direct the healing into a more-regenerative/less-scarring pathway.

Scarless wound healing: finding the right cells and signals

“…Utilization of physiological anti-inflammatory molecules offers the potential to direct wound healing down regenerative pathways. For example, systemic administration of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) led to a more regenerative healing process characterized by less macroscopic scar formation as well as organization of collagen fibers more closely mimicking unwounded skin (de Souza, et al, 2015). While this effect required administration of α-MSH prior to wounding, prophylactic administration of anti-fibrotic agents is not without clinical utility, particularly in cases such as scar revision surgery.…”

The role of aldo‐keto reductase 1C3 (AKR1C3)‐mediated prostaglandin D2 (PGD2) metabolism in keloids

“…For example, some studies reported direct contact of mast cells with myofibroblasts within the fibrotic lesion of keloids suggesting the existence of a crosstalk between the two cell populations that may promote keloid progression . Also, reduced mast cell count has been associated with improved skin wound healing as reflected by reduced scarring and improved collagen organization shown in a cutaneous healing model in mice .…”

Active Nanofibrous Membrane Effects on Gingival Cell Inflammatory Response

“…An inhibition of melanoma cell migration by α-MSH has been also observed in another inflammatory context [23]. Therefore, cell modulation of proliferation and migration by α-MSH may play a role in the anti- s oft tissues invasion and anti-fibrotic effects into the wound site [10]. …”

“…The anti-inflammatory properties of alpha-melanocyte stimulating hormone (α-MSH) have recently been demonstrated during cutaneous wound healing in vivo [10] and in dental pulp fibroblasts stimulated by Porphyromonas gingivalis lipopolysaccharide ( Pg -LPS) in vitro [11]. α-MSH is an endogenous 13 amino acid neuropeptide derived from proteolytic cleavage of pro-opiomelanocortin hormone, which is synthesized by normal human keratinocytes and melanocytes [12].…”