Subject(s)
Polymorphism, Genetic , Psoriasis/genetics , Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics , Adaptor Proteins, Signal Transducing , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Dermatitis, Atopic/genetics , Female , Humans , Male , Middle AgedSubject(s)
Interleukins/genetics , Polymorphism, Genetic , Psoriasis/ethnology , Psoriasis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Asian People , Child , Female , Genotype , Humans , Japan , Male , Middle Aged , Polymorphism, Single Nucleotide , Young Adult , Interleukin-22ABSTRACT
Diabetic patients are at high risk of developing delayed cutaneous wound healing. Adiponectin plays a pivotal role in the pathogenesis of diabetes and is considered to be involved in various pathological conditions associated with diabetes; however, its role in wound repair is unknown. In this study, we elucidated the involvement of adiponectin in cutaneous wound healing in vitro and in vivo. Normal human keratinocytes expressed adiponectin receptors, and adiponectin enhanced proliferation and migration of keratinocytes in vitro. This proliferative and migratory effect of adiponectin was mediated via AdipoR1/AdipoR2 and the ERK signaling pathway. Consistent with in vitro results, wound closure was significantly delayed in adiponectin-deficient mice compared with wild-type mice, and more importantly, keratinocyte proliferation and migration during wound repair were also impaired in adiponectin-deficient mice. Furthermore, both systemic and topical administration of adiponectin ameliorated impaired wound healing in adiponectin-deficient and diabetic db/db mice, respectively. Collectively, these results indicate that adiponectin is a potent mediator in the regulation of cutaneous wound healing. We propose that upregulation of systemic and/or local adiponectin levels is a potential and very promising therapeutic approach for dealing with diabetic wounds.
Subject(s)
Adiponectin/physiology , Cell Movement/immunology , Cell Proliferation , Keratinocytes/immunology , MAP Kinase Signaling System/immunology , Skin/immunology , Wound Healing/immunology , Adiponectin/biosynthesis , Adiponectin/deficiency , Animals , Cell Movement/genetics , Cells, Cultured , Diabetes Mellitus/enzymology , Diabetes Mellitus/immunology , Diabetes Mellitus/pathology , Humans , Keratinocytes/enzymology , Keratinocytes/pathology , MAP Kinase Signaling System/genetics , Mice , Mice, Knockout , Mice, Obese , Receptors, Adiponectin/biosynthesis , Receptors, Adiponectin/physiology , Skin/enzymology , Skin/pathology , Up-Regulation/genetics , Up-Regulation/immunology , Wound Healing/geneticsABSTRACT
BACKGROUND: Some chemokines are known to accelerate wound healing. However, there has been no report on the relationship between Thymus and activation-regulated chemokine (TARC)/CC chemokine ligand (CCL) 17 and wound healing. The purpose of this study was to determine whether CCL17 enhances response to cutaneous injury. METHODS: We made a full-thickness dorsal wound in transgenic (Tg) mice, in which CCL17 was overexpressed and in control mice. Wound size was compared over the course of time. We evaluated the effect of CCL17 on fibroblast migration by a Boyden chamber assay and a scratch wound assay. RESULTS: Wound closure in Tg mice was more accelerated than in control mice. CCL17 enhanced nerve growth factor (NGF) production by 2B4, which is mouse T cell hybridoma. Further, in the wound area of Tg mice, the number of CCR4(+) fibroblasts, CCR4(+) lymphocytes and mast cells was increased compared to control mice, as was the number of NGF(+) lymphocytes around the wound area. In vitro assay, CCL17 was shown to enhance the migration of fibroblasts. CONCLUSION: These results suggest that CCL17 accelerates wound healing, mainly by enhancing fibroblast migration, and possibly by increasing NGF(+) lymphocytes and mast cells, which have independently been reported to enhance wound healing.
