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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02421

A Frog-derived Immunomodulatory Peptide Promotes Cutaneous Wound Healing By Regulating Damage Response

 Xiaoqin He1, 2, Yang Yang1, Lixian Mu3, Yandong Zhou1, Yue Chen1, Jing Wu3, Yipeng Wang4, Hialong Yang3,  Min Li1,  Wei Xu1* and  Lin Wei1*
  • 1Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, China
  • 2Jiangsu Institute of Parasitic Diseases (JIPD), China
  • 3School of Basic Medicine, Kunming Medical University, China
  • 4Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, China

Wound healing-promoting peptides exhibit excellent therapeutic potential in regenerative medicine. However, amphibian-derived wound healing-promoting peptides and their mechanism of action remain to be further elucidated. We hereby characterized a novel wound healing-promoting peptide, Ot-WHP, derived from Chinese concave-eared frog Odorrana tormota. It efficiently promoted wound healing in a mouse model of full-thickness wounds. Ot-WHP significantly increased the number of neutrophils in wounds, and modestly promoted neutrophil phagocytosis and phorbol myristate acetate (PMA)-induced neutrophil extracellular trap formation. Ot-WHP also significantly increased the number of macrophages in wound sites, and directly induced chemokine, cytokine and growth factor production in macrophages by activating mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signaling pathways. Of note, Ot-WHP did not act as a chemoattractant for neutrophils and macrophages, suggesting its chemotactic activity depends on inducing chemoattractant production in macrophages. Besides, Ot-WHP directly promoted keratinocyte migration by enhancing integrin expression and cell adhesion. In addition, Ot-WHP significantly enhanced the cross-talk between macrophages and keratinocytes/fibroblasts by promoting keratinocyte/fibroblast proliferation, and fibroblast-to-myofibroblast transition despite of no direct effects on keratinocyte/fibroblast proliferation, and fibroblast differentiation. Collectively, Ot-WHP directly elicited the production of regulatory factors in macrophages, consequently initiated and accelerated the inflammatory phase by recruiting neutrophils and macrophages to wounds, in turn enhanced the cross-talk between macrophages and keratinocytes/fibroblasts, additionally promoted keratinocyte migration, and finally promoted cutaneous wound healing. Our findings provide a promising immunomodulator for acute wound management and new clues for understanding the mechanism of action of amphibian-derived wound-promoting peptides.

Keywords: Immunomodulatory peptide, Wound Healing, amphibian, Odorrana tormota, Skin

Received: 19 Jul 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 He, Yang, Mu, Zhou, Chen, Wu, Wang, Yang, Li, Xu and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Wei Xu, Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China, xuweifd828@126.com
Dr. Lin Wei, Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China, weilin1005@126.com