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Leptin promotes wound healing in the skin

Significance statement

Leptin, a 16-kDa non-glycosylated polypeptide anti-obesity hormone, is a product of the obese (ob) gene. Some past studies unveiled the effect of leptin on would healing by demonstrating that leptin acted as an autocrine/paracrine regulator in the wounded sites and that skin would healing delayed in leptin deficient ob/ob mice. These findings strongly suggest the possibility that leptin could be a potential medicine for promoting wound healing. In the present study, the authors investigated whether leptin exerted a promotive influence on the skin would healing even when administered with a low single dosage and one time by using MedGel, a bioabsorbable hydrogel used for a drug delivery system (DDS). First, the expression/localization of leptin receptor (Ob-R) in mouse and human skin was immunohistochemically confirmed. Some epithelial cells of hair follicles were also positive for Ob-R. This finding suggests that epidermal cells and hair follicle cells are target cells of leptin. The area of the wound created in mouse back skin decreased with time much faster in the leptin-treated group. Significantly more blood vessels were distributed in the connective tissue beneath the ulcer in the leptin-treated group. Moreover, leptin showed modest stimulatory effect on the proliferation of human epidermal keratinocytes. Quantitative RT-PCR analysis detected an elevated expression of mRNA encoding Cytokeratin 13, Cytokeratin 14, and Transglutaminase I of human epidermal keratinocytes in the presence of exogenous leptin. An in vitro wound healing assay also revealed that leptin promoted the migration of keratinocytes. This study demonstrated for the first time that topically administered leptin is capable of accelerating wound healing in the skin by promoting angiogenesis around the wounded area and by enhancing the proliferation, differentiation/function and migration of epidermal keratinocytes. Moreover, this study also clearly demonstrated that leptin is effective for wound healing acceleration even in a single dose when applied topically by using an adequate drug delivery system. These findings are considered to pave the way for the clinical utilization of leptin as a wound healing-promoting agent especially in the treatment and/or prevention of decubital ulcers of increasing elderly patients with poor ADL.

Figure legend

Effect of leptin on wound healing in the skin. (A) Chemical wounds were created in mouse back skin by applying two pieces of filter paper (12x12mm each) soaked with 20% sodium hypochlorite for 5 minutes. Wound formation was verified next day, and the wounds were covered with 15 g (12 x 12 x 1 mm) of MedGel containing 10 ml of 100 ng/ml leptin or PBS. At day 8 after wound creation, significantly enhanced re-epithelialization of the wound was observed in leptin-treated group compared with control group. (B) Histological findings at day 8 after wound creation. Spaces between two arrowheads show ulcerated area without epithelial lining. Scale bars = 500 mm.Leptin Promotes Wound Healing in the Skin. Global Medical Discovery

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Journal Reference

Tadokoro S, Ide S, Tokuyama R, Umeki H, Tatehara S, Kataoka S, Satomura K. PLoS One. 2015; 10(3):e0121242.

Department of Oral Medicine and Stomatology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan.

Abstract

INTRODUCTION:

Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.

METHODS:

Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptinwas topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of woundrepair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.

RESULTS:

Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.

CONCLUSION:

Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.

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