Impact of Elastin-Derived Peptide VGVAPG on Matrix Metalloprotease-2 and -9 and the Tissue Inhibitor of Metalloproteinase-1, -2, -3 and -4 mRNA Expression in Mouse Cortical Glial Cells In Vitro

Konrad A. Szychowski , Anna Wójtowicz , Jan Gmiński

Abstract

Degradation products of elastin, i.e. elastin-derived peptides (EDPs), are involved in various physiological and pathological processes. EDPs are detectable in cerebrospinal fluid in healthy people and in patients after ischemic stroke. However, to date, no studies concerning the role of EDP in the nervous system were conducted. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important roles during the repair phases of cerebral ischemia, particularly during angiogenesis and reestablishment of cerebral blood flow. Therefore, the aim of this study was to investigate the impact of the specific elastin-derived peptide VGVAPG on Mmp-2, -9 and Timp-1, -2, -3 and -4 mRNA expression in mouse cortical glial cells in vitro. Primary glial cells were maintained in DMEM/F12 without phenol red supplemented with 10% fetal bovine serum and the cells were exposed to 50 nM, 1 and 50 μM of the VGVAPG peptide. After 3 and 6 h of exposition to the peptide, expression of Mmp-2, -9 and Timp-1, -2, -3 and -4 mRNA was measured. Moreover, siRNA gene knockdown, cytotoxicity and apoptosis measurement were included in our experiments, which showed that VGVAPG in a wide range of concentrations exhibited neither proapoptotic nor cytotoxic properties in mouse glial cells in vitro. The peptides enhanced mRNA expression of Timp-2 and Timp-3 genes in an elastin-binding protein (EBP)-dependent manner. However, changes in mRNA expression of Mmp-2, Mmp-9 and Timp-4 were partially EBP-dependent. The decrease in mRNA expression of Timp-1 was EBP-independent. However, further studies underlying the VGVAPG peptide’s mechanism of action in the nervous system are necessary.
Author Konrad A. Szychowski
Konrad A. Szychowski,,
-
, Anna Wójtowicz (FoAS / IoAS)
Anna Wójtowicz,,
- Institute of Animal Science
, Jan Gmiński
Jan Gmiński,,
-
Journal seriesNeurotoxicity Research, ISSN 1029-8428, e-ISSN 1476-3524, (N/A 70 pkt)
Issue year2019
Vol35
No1
Pages100-110
Publication size in sheets0.5
Keywords in EnglishElastin-derived peptides, VGVAPG, Glial cells, MMP-2, MMP-9, TIMPs
ASJC Classification2800 General Neuroscience; 3005 Toxicology
DOIDOI:10.1007/s12640-018-9935-x
URL https://link.springer.com/content/pdf/10.1007%2Fs12640-018-9935-x.pdf
Internal identifierWHiBZ/2019/5
Languageen angielski
LicenseJournal (articles only); author's original; Uznanie Autorstwa (CC-BY); after publication
File
Szychowski2019_Article_ImpactOfElastin-DerivedPeptide.pdf 1,08 MB
Score (nominal)70
Score sourcejournalList
Publication indicators WoS Citations = 3; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.823; WoS Impact Factor: 2018 = 3.311 (2) - 2018=3.245 (5)
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