Are melanocortin peptides future therapeutics for cutaneous wound healing?

Abstract

Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α‐melanocyte‐stimulating hormone (α‐MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated α‐MSH peptides such as Lys‐Pro‐Val (KPV) as well as derivatives like Lys‐d‐Pro‐Thr (KdPT), the latter containing the amino acid sequence 193‐195 of interleukin‐1β, have been found to possess anti‐inflammatory effects but to lack the pigment‐inducing activity of α‐MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so‐far available data on melanocortin peptides and derivatives in wound healing.

Discovery of a Highly Selective MC1R Agonists Pentapeptide to Be Used as a Skin Pigmentation Enhancer and with Potential Anti-Aging Properties

“…The alpha-MSH-MC1R signaling system has many diverse biological effects. Among these described effects are, for example, cutaneous wound healing [64], effects on the immune system [65] or nucleotide excision repair [31,66], but these were not investigated in this study.…”

Autonomic nerve dysfunction and impaired diabetic wound healing: The role of neuropeptides

“…Furthermore, intraperitoneal injection of a-MSH prior to injury led to significant reduction of leukocytes and mast cells in the granulation tissue of mice 3 and 7 days post-wounding and reduced scar area and collagen fiber organization on day 40 after injury (de Souza et al, 2015). Hence, it appears that a-MSH influences inflammatory pathways and its presence in the skin and involvement in various functions of different skin cell types makes it an attractive target for additional cutaneous diabetic wound healing studies (Bohm and Luger, 2019).…”

Current and emerging treatments targeting the neuroendocrine system for disorders of the skin and its appendages

“…[35] Different α-MSH analogs and derivatives have been investigated for the treatment of various conditions including acne vulgaris, photosensitivity, chronic skin ulcers, ulcerative colitis and psoriasis. [38][39][40] Afamelanotide ([Nle 4 -D-Phe 7 ]-α-MSH), a super-potent and long-lasting α-MSH analog, [41] induces melanization in vitro and in vivo. [42] Since melanin production decreases penetration of UV radiation, afamelanotide was tested for the prevention of the photosensitivity disorder solar urticaria.…”