title: Leucine-enkephalin promotes wound repair through the regulation of hemidesmosome dynamics and matrix metalloprotease.
abstract: 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, P90(RSK), 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 P90(RSK) and Elk-1 and significantly blunted wound repair. Therefore, our results suggest that activation of Erk and its downstream effectors, P90(RSK) and Elk-1, are critical for DOPr-mediated skin homeostasis.
authors.affiliation: Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea.
authors.forename: Dong Joo
authors.initials: DJ
authors.lastname: Yang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 52828, Republic of Korea.
authors.forename: Kyung Suk
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea.
authors.forename: Chang Mann
authors.initials: CM
authors.lastname: Ko
authors.affiliation: Anti-aging Research Institute of BIO-FD&C Co. Ltd., Incheon 21990, Republic of Korea.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Moh
authors.affiliation: Anti-aging Research Institute of BIO-FD&C Co. Ltd., Incheon 21990, Republic of Korea.
authors.forename: Jihyeok
authors.initials: J
authors.lastname: Song
authors.affiliation: Derma-Lucia Skinceuticals LLC, 7500 Escala Drive, Austin, TX 78735, USA.
authors.forename: Lucia C
authors.initials: LC
authors.lastname: Hur
authors.affiliation: Department of Plastic and Reconstructive Surgery, Gachon University Gil Medical Center, Gachon University, School of Medicine, 1198 Guwol-Dong, Namdong-Gu, Incheon 21565, Republic of Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Cheon
authors.affiliation: Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Anti-aging Research Institute of BIO-FD&C Co. Ltd., Incheon 21990, Republic of Korea. Electronic address: imyunhee@gmail.com.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea. Electronic address: kiwoo@yonsei.ac.kr.
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D004743:Enkephalin, Leucine / Q000502:physiology*; D022002:Hemidesmosomes / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D020935:MAP Kinase Signaling System; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D004743:Enkephalin, Leucine; D020782:Matrix Metalloproteinases
keywords: Hemidesmosome; Leucine-enkephalin; Wound healing; δ-Opioid receptor