Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
J Immunol. 2012 Sep 15;189(6):3231-41. doi: 10.4049/jimmunol.1101739. Epub 2012 Aug 17.
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.
糖尿病患者发生延迟性皮肤伤口愈合的风险很高。脂联素在糖尿病发病机制中起关键作用，被认为与糖尿病相关的各种病理状况有关；然而，其在伤口修复中的作用尚不清楚。在这项研究中，我们阐明了脂联素在体外和体内皮肤伤口愈合中的作用。正常的人角质形成细胞表达脂联素受体，脂联素增强了体外角质形成细胞的增殖和迁移。脂联素的这种增殖和迁移作用是通过 AdipoR1/AdipoR2 和 ERK 信号通路介导的。与体外结果一致的是，与野生型小鼠相比，脂联素缺乏型小鼠的伤口闭合明显延迟，更重要的是，脂联素缺乏型小鼠在伤口修复过程中的角质形成细胞增殖和迁移也受损。此外，全身性和局部给予脂联素分别改善了脂联素缺乏型和糖尿病 db/db 小鼠的受损伤口愈合。总之，这些结果表明脂联素是调节皮肤伤口愈合的有力介质。我们提出，上调全身和/或局部脂联素水平是治疗糖尿病性伤口的一种有潜力和很有前途的治疗方法。
