Adiponectin regulates cutaneous wound healing by promoting keratinocyte proliferation and migration via the ERK signaling pathway

• Published in: The Journal of immunology (1950) 2012-09, Vol.189 (6), p.3231-3241
• Main Authors: Shibata, Sayaka, Tada, Yayoi, Asano, Yoshihide, Hau, Carren S, Kato, Toyoaki, Saeki, Hidehisa, Yamauchi, Toshimasa, Kubota, Naoto, Kadowaki, Takashi, Sato, Shinichi
• Format: Article
• Language: English
• Subjects: Adiponectin - biosynthesis; Adiponectin - deficiency; Adiponectin - physiology; Animals; Cell Movement - genetics; Cell Movement - immunology; Cell Proliferation; Cells, Cultured; Diabetes Mellitus - enzymology; Diabetes Mellitus - immunology; Diabetes Mellitus - pathology; Humans; Keratinocytes - enzymology; Keratinocytes - immunology; Keratinocytes - pathology; MAP Kinase Signaling System - genetics; MAP Kinase Signaling System - immunology; Mice; Mice, Knockout; Mice, Obese; Receptors, Adiponectin - biosynthesis; Receptors, Adiponectin - physiology; Skin - enzymology; Skin - immunology; Skin - pathology; Up-Regulation - genetics; Up-Regulation - immunology; Wound Healing - genetics; Wound Healing - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101739

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.