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This article is part of the Research Topic

Skin Functions and Mechanisms

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

Front. Physiol. | doi: 10.3389/fphys.2019.00024

High glucose suppresses keratinocyte migration through the inhibition of p38 MAPK/autophagy pathway

 Lingfei Li1, 2,  Junhui Zhang1, 2, Qiong Zhang1, 2, Dongxia Zhang1, 2, Fei Xiang1, 2, Jiezhi Jia1, 2, Ping Wei3, Jiaping Zhang4, Jiongyu Hu1, 3* and Yuesheng Huang1, 2*
  • 1State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, China
  • 2Institute of Burn Research, Southwest Hospital, Third Military Medical University, China
  • 3Department of Endocrinology, Southwest Hospital, Third Military Medical University, China
  • 4Southwest Plastic Surgery Hospital, Army Medical University, China

Wound healing is delayed frequently in patients with diabetes. Proper keratinocyte migration is an essential step during re-epithelialization. Impaired keratinocyte migration is a critical underlying factor responsible for the delayed wound healing in patients with diabetes, which is mainly attributed to the hyperglycemic state. However, the underlying mechanisms remain largely unknown. Previously, we demonstrated a marked activation of p38/MAPK pathway in the regenerated migrating epidermis, which in turn promoted keratinocyte migration. In the present study, we find that p38/MAPK pathway is downregulated and accompanied by inactivation of autophagy under high glucose environment. In addition, we demonstrate that inactivation of p38/MAPK and autophagy result in the inhibition of keratinocyte migration under high glucose environment, and the activating p38/MAPK by MKK6(Glu) overexpression rescues cell migration through an autophagy-dependent way. Moreover, diabetic wound epidermis shows a significant inhibition of p38/MAPK and autophagy. Targeting these dysfunctions may provide novel therapeutic approaches

Keywords: Autophagy, p38/MAPK, cell migration, high glucose, diabetes

Received: 01 Nov 2018; Accepted: 10 Jan 2019.

Edited by:

Luis Monteiro Rodrigues, Universidade Lusófona, Portugal

Reviewed by:

Darius J. Lane, Florey Institute of Neuroscience and Mental Health, Australia
Sumit Sahni, University of Sydney, Australia  

Copyright: © 2019 Li, Zhang, Zhang, Zhang, Xiang, Jia, Wei, Zhang, Hu and Huang. 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. Jiongyu Hu, Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China, jiongyuhu@163.com
Prof. Yuesheng Huang, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China, yshuang1958@163.com