Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Institute of Convergence Science, Korea University, Seoul 136-701, Korea.
Int J Mol Sci. 2018 Nov 19;19(11):3642. doi: 10.3390/ijms19113642.
Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.
内脏脂肪素是脂肪因子家族的一员，在许多代谢和应激反应中发挥重要作用。内脏脂肪素有直接治疗作用的机制尚未见报道。在这项研究中，我们研究了内脏脂肪素对体外和体内伤口愈合的影响。内脏脂肪素增强了人真皮成纤维细胞（HDF）和角质形成细胞的增殖和迁移，并在体外和体内促进了与伤口愈合相关的血管内皮生长因子（VEGF）的表达。内脏脂肪素处理 HDF 可在时间依赖性方式下激活细胞外信号调节激酶 1 和 2（ERK1/2）和 c-Jun N-末端激酶 1 和 2（JNK1/2）。ERK1/2 和 JNK1/2 的抑制导致内脏脂肪素诱导的 HDF 增殖和迁移显著减少。重要的是，用其中和抗体阻断 VEGF 抑制了内脏脂肪素诱导的 HDF 和人角质形成细胞的增殖和迁移，表明内脏脂肪素通过增加 VEGF 的表达来诱导 HDF 和人角质形成细胞的增殖和迁移。此外，内脏脂肪素有效地改善了体内伤口修复，与表皮生长因子（EGF）的伤口愈合活性相当。总之，我们证明了内脏脂肪素通过诱导 VEGF 的表达来促进 HDF 和人角质形成细胞的增殖和迁移，并且可以作为伤口愈合的潜在新型治疗剂。
