Preprint Article Version 1 This version is not peer-reviewed

Visfatin Promotes Wound Healing Through the Activation of ERK1/2 and JNK1/2 Pathway

Version 1 : Received: 24 October 2018 / Approved: 29 October 2018 / Online: 29 October 2018 (09:54:28 CET)

A peer-reviewed article of this Preprint also exists.

Lee, B.-C.; Song, J.; Lee, A.; Cho, D.; Kim, T.S. Visfatin Promotes Wound Healing through the Activation of ERK1/2 and JNK1/2 Pathway. Int. J. Mol. Sci. 2018, 19, 3642. Lee, B.-C.; Song, J.; Lee, A.; Cho, D.; Kim, T.S. Visfatin Promotes Wound Healing through the Activation of ERK1/2 and JNK1/2 Pathway. Int. J. Mol. Sci. 2018, 19, 3642.

Journal reference: Int. J. Mol. Sci. 2018, 19, 3642
DOI: 10.3390/ijms19113642

Abstract

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, and significantly increased 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.

Subject Areas

visfatin; wound healing; VEGF; MAPK

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