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Smad‐induced alterations of matrix metabolism by a myristoyl tetra peptide
Author(s) -
Kwon Haeyoung,
Lee Yun Sub,
Kim Myung Ok,
Chang Min Youl,
Won Bo Mi,
Jin Byung Suk,
Park Seyeon
Publication year - 2014
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3070
Subject(s) - smad , mmp1 , extracellular matrix , timp1 , microbiology and biotechnology , signal transduction , chemistry , gene expression , transforming growth factor , matrix metalloproteinase , biology , biochemistry , gene
Regulation of extracellular matrix (ECM) components is essential for tissue homeostasis and function. We screened a small peptide that induces ECM protein synthesis for its usefulness in protecting keratinocytes. In this report, we demonstrate that myristoyl tetrapeptide Ala‐Ala‐Pro‐Val (mAAPV) stimulates the expression of ECM proteins and inhibits the expression of metalloproteinases (MMPs) that degrade ECM proteins in Hs68 human fibroblast cells. In order to elucidate the underlying molecular mechanisms for the effects of mAAVP, we investigated the changes in gene expression in the presence of mAAPV using a cDNA microarray. Treatment with mAAPV resulted in decreased expression of MMP‐related genes such as MMP1 , MMP3 , TIMP1 and TIMP3 and increased expression of collagen genes, including COL1A1 , COL1A2 , COL3A1 , COL5A1 and COL6A3 . The pattern of gene expression regulated by mAAPV was very similar to that of gene expression induced by transforming growth factor (TGF)‐ β , indicating that the TGF‐ β signaling pathway is crucial for simultaneous activation of several ECM‐related genes by mAAPV. We examined whether the activation of SMAD, a downstream protein of TGF‐ β receptor, is involved in the signal transduction pathway induced by mAAPV. The results demonstrate that mAAVP directly activates SMAD2 and induces SMAD3 to bind to DNA. In conclusion, our results demonstrate that mAAPV both enhances the expression of collagen and inhibits its degradation via production of protease inhibitors that prevent enzymatic breakdown of the ECM. The results suggest that mAAPV would be a useful ECM‐protecting agent. Copyright © 2014 John Wiley & Sons, Ltd.