Trehalose promotes wound healing in vitro by enhancing the migration of human keratinocytes via the VEGF/JNK/PI3K pathway

Background

Trehalose is a naturally occurring disaccharide found in invertebrates but cannot be synthesized by vertebrates. We previously reported that high-concentration trehalose induces a transient senescent-like state in fibroblasts, leading to cell cycle arrest and growth factor secretion via CDKN1A/p21, and this process promoted keratinocyte proliferation, enhancing capillary formation and wound closure in vivo .

Objective

This study aimed to investigate the effect of trehalose on human keratinocytes.

Methods

Previously published RNA-seq data of cytokine-untreated samples from our group of trehalose-treated human keratinocytes were re-analyzed, and an in vitro scratch assay was performed using cells treated with mitomycin C.

Results

The trehalose-treated group exhibited increased wound closure. A significantly increased secretion of vascular endothelial growth factor (VEGF) was observed in keratinocytes treated with high-concentration trehalose, which is one of the most crucial molecules inducing angiogenesis in the skin. Significant upregulation of mRNA level and protein secretion of VEGF was confirmed using qPCR and ELISA, respectively. Furthermore, treatment with axitinib, a VEGF receptor inhibitor, significantly suppressed trehalose-induced activation of keratinocyte migration. Additionally, the increase in trehalose-induced migration activity was significantly inhibited by the Jun N-terminal kinase (JNK) inhibitor SP600125 and the PI3K inhibitor LY294002.

Conclusion

Trehalose promotes wound healing via VEGF secretion from keratinocytes and the PI3K and JNK pathways. The findings of this study may lead to the development of novel therapeutic agents that can alter the wound healing process.

IMPORTANT

• Manuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way.

• Upon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor.

• The identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report.

• The identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred.

GUIDELINES

• For reviewers: https://www.reviewcommons.org/reviewers

• For authors: https://www.reviewcommons.org/authors

CONTACT

The Review Commons office can be contacted directly at: office@reviewcommons.org