Leucine-enkephalin promotes wound repair through the regulation of hemidesmosome dynamics and matrix metalloprotease

Dong Joo Yang, Kyung Suk Lee, Chang Mann Ko, Sang Hyun Moh, Jihyeok Song, Lucia C. Hur, Young Woo Cheon, Seung Ho Yang, Yun Hee Choi, Ki Woo Kim

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


The skin responds to environmental stressors by coordinated actions of neuropeptides and their receptors. An endogenous peptide for δ-opioid receptor (DOPr), Leu-enkephalin (L-ENK), is expressed in the skin and its expression is altered in pathological conditions. Although the importance of DOPr is rapidly gaining recognition, the molecular mechanisms underlying its effects on wound healing are largely undefined. We show here that L-ENK induced activation of Erk, P90RSK, and Elk-1 and promoted the disruption of hemidesmosomes and the expression of matrix metalloprotease (MMP)-2 and MMP-9, important processes for wound healing. Treatment with Erk inhibitor blocked activation of P90RSK and Elk-1 and significantly blunted wound repair. Therefore, our results suggest that activation of Erk and its downstream effectors, P90RSK and Elk-1, are critical for DOPr-mediated skin homeostasis.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
Publication statusPublished - 2016 Feb

Bibliographical note

Funding Information:
We would like to thank Ann W. Kinyua (Yonsei University) for the critical reading of this manuscript. This research was supported by Gachon University Gil Medical Center Grant 2013-41 for Y.W.C., Global PhD Fellowship Program ( NRF-2015H1A2A1032009 ) for D.J.Y., Small and Medium Business Administration (Technological Innovation R&D Program S2178403 ) for S.H.M., and the National Research Foundation ( NRF-2013R1A1A1007693 and 2014K1A3A1A19066980 ) for K.W.K.

Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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