Inhibition of UV-induced matrix metabolism by a myristoyl tetrapeptide.
Regulation of extracellular matrix (ECM) composition is important in tissue homeostasis and function. We screened small peptides for their ability to inhibit ultraviolet (UV)-induced cell metabolism in epidermal fibroblasts. We found that UV irradiation increased matrix metalloproteinase (MMP) expression and inflammatory gene expression in human Hs68 fibroblast cells. We also demonstrated that a myristoyl tetrapeptide with the amino acid sequence Gly-Leu-Phe-Trp (mGLFW) suppressed the UV-induced expression of MMPs and inflammatory genes. Moreover, mGLFW stimulated the expression of ECM proteins in Hs68 fibroblasts. In order to provide the mechanism of action for mGLFW, we investigated UV-induced signaling changes in the presence of mGLFW using a cDNA microarray. UV exposure increased the expression of MMP genes, such as MMP1, MMP3, and MMP14, and inflammation-related genes, including interleukin 1 receptor and peroxisome proliferator-activated receptor gamma (PPARγ). Treatment with mGLFW abrogated the UV-induced expression of MMP-related genes and inflammatory genes. In addition, mGLFW increased the expression of collagen genes, including COL1A1, COL1A2, and COL5A1. We examined whether the activation of AP-1, a UV-activated transcription factor, is suppressed by mGLFW. The results demonstrated that AP-1 expression increased upon UV exposure and that this expression was inhibited by mGLFW. In conclusion, our results demonstrate that mGLFW reversed the effects of UV exposure by enhancing the expression of collagen proteins and suppressing the expression of MMPs, which degrade the ECM.
Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea.
Haeyoung
H
Kwon
Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea.
Eunsook
E
Ahn
Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea.
Seon-Young
SY
Kim
Miwon Commercial Co. Ltd., Ansan, Korea.
YeoHong
Y
Kang
Miwon Commercial Co. Ltd., Ansan, Korea.
Myung Ok
MO
Kim
Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea.
Byung Suk
BS
Jin
Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea.
Seyeon
S
Park
D000595:Amino Acid Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays
D016207:Cytokines; D009842:Oligopeptides; D047495:PPAR gamma; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D003094:Collagen; D004247:DNA; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
MMPs; microarray; myristoyl tetrapeptide; procollagen