Abstract
IntroductionLeptin, 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.MethodsImmunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair 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.ResultsOb-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.ConclusionTopically 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.
Highlights
Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties
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
The product of ob(obese) gene, is a 16 kDa non-glycosylated polypeptide anti-obesity hormone mainly produced and secreted by adipose tissues [1]
Summary
Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated. The study was approved by the Research Ethics Review Committee of Tsurumi University School of Dental Medicine (approval number: 1048). The tissues were fixed with 10 N Mildform (Wako Pure Chemical Industries Ltd, Osaka, Japan), and embedded in paraffin. The animal care and experimental protocols were approved by the Committee on the Ethics of Animal Experiments of Tsurumi University (approval number: 24A064). All surgery was performed under general anesthesia by intraperitoneal injection of 40 mg/kg pentobarbital sodium, and all efforts were made to minimize suffering. Eighteen 6-week-old male ICR mice were obtained from CLEA Japan, Inc. (Tokyo, Japan), fed a normal diet and maintained under a
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