Untersuchungen zur biologischen Rolle der Matrixmetalloproteinase MMP-19

Mauch, Simon

Untersuchungen zur biologischen Rolle der Matrixmetalloproteinase MMP-19

Dateien

Diss_SM.pdfGröße: 3.07 MBDownloads: 1014

Datum

2000

Autor:innen

Mauch, Simon

URI (zitierfähiger Link)

http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-6449

Link zur Lizenz

Urheberrechtlich geschützt

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Titel in einer weiteren Sprache

Analysis of the biological function of the matrix metalloproteinase MMP-19

Publikationstyp

Dissertation

Publikationsstatus

Published

Zusammenfassung

Matrix metalloproteinases (MMP) comprise a family of extracellular matrix degrading enzymes playing pivotal roles in embryonic development and growth as well as tissue remodeling and repair. Inappropriate expression of MMP may contribute to the pathogenesis of many tissue-destructive processes, including both highly prevalent diseases such as arthritis, MS, and tooth decay, as well as the leading causes of death in developed countries: cardiovascular diseases, tumor progression, and chronic obstructive pulmonary diseases.
MMP-19 had been isolated by the author as an autoantigen associated with rheumatoid arthritis called RASI-1. Phylogenetically MMP-19 seems to be an ancestral member of the MMP family. The enzymatic substrates recognized by MMP-19 may be highly specific since the domains responsible for substrate specificity in MMP-19 differ from all other MMP.
MMP-19 is expressed both in blood vessels and myleoid cells. It has been shown that adhesion during myleoid differentiation leads to upregulation of MMP-19 gene expression. These and other data indicate that MMP-19 function may play a role in macrophage migration. Taken into account that MMP-19 is also expressed in smooth muscle cells MMP-19 may contribute to atherosclerotic vessel malformation.
The expression of MMP-19 in micro-, but not macrovascular endothelial cells suggests that MMP-19 is a factor in early angioprocesses. Upregulation of MMP-19 mRNA levels upon angiogenetic stimuli support this view.
The MMP-19 protein is not covalently attached to the surface of myeloid cells. It coprecipitates with two cell surface proteins. The attachment is mediated by the C-terminal hemopexin-like domain. In the yeast two hybrid system MMP-19 interacts with Rapa, a novel protein. Rapa does not show any significant similarity to known proteins. Primary structure analyses indicate that Rapa might contribute to cellular structures. In vitro data showed the interaction between Rapa and MMP-19.

Zusammenfassung in einer weiteren Sprache

Matrixmetalloproteinasen (MMP) sind Extrazellulärmatrix-degradierende Enzyme mit zentralen Rollen bei Embryonalentwicklung, Gewebsumbau und -reparatur. Missexpression trägt zur Pathologie vieler gewebszerstörender Prozesse bei. Hierzu gehören sowohl Erkrankungen hoher Prävalenz wie Arthritis, MS und Zahnverfall, als auch die wichtigsten Todesursachen in entwickelten Ländern: Kardiovaskuläre Erkrankungen, Tumore und chronische Lungenerkrankungen.
MMP-19 wurde vom Autor als das mit Rheumatoider Arthritis assoziierte Autoantigen RASI-1 isoliert und ist als phylogenetische Frühform der MMP zu betrachten. Die von MMP-19 erkannten Substrate unterscheiden sich wahrscheinlich von denen anderer MMP, da die Differenz in den hierfür relevanten Domänen groß ist.
MMP-19 wird sowohl in myeloiden als auch in Blutgefäßzellen exprimiert. Eine adhäsionsabhängige Expressionsinduktion während der myeloiden Differenzierung wurde gezeigt. Diese und weitere Daten deuten auf eine Funktion bei der Makrophagenmigration. Zusammen mit der ebenso gezeigten Expression in Zellen der glatten Gefäßmuskulatur weisen die Daten auf eine Rolle bei arteriosklerotischen Gefäßveränderungen. MMP-19 scheint des weiteren bei frühen angiogenetischen Vorgängen beteiligt, da MMP-19 zwar in mikro-, nicht jedoch in makrovaskulären Endothelzellen exprimiert wird. Proangiogenetische Stimuli erhöhen die MMP-19 Expression.
Das Protein MMP-19 ist nicht kovalent auf der Oberfläche myeloider Zellen verankert und kopräzipitiert mit zwei Oberflächenproteinen. Diese Bindung wird durch die C-terminale Hämopexin-ähnliche Domäne vermittelt. Im Yeast Two-Hybrid System interagiert MMP-19 mit dem bislang unbekannten Protein Rapa. Rapa zeigt keine signifikante Ähnlichkeit zu bekannten Proteinen, die Analyse der Primärstruktur lässt es als mögliches Strukturprotein erscheinen. Die Interaktion von Rapa mit MMP-19 wurde in vitro bestätigt.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Matrixmetalloproteinase, MMP-19, Rasi, Angiogenese, matrix metalloproteinse, MMP-19, Rasi, angiogenesis

Zitieren

ISO 690

MAUCH, Simon, 2000. Untersuchungen zur biologischen Rolle der Matrixmetalloproteinase MMP-19 [Dissertation]. Konstanz: University of Konstanz

BibTex

@phdthesis{Mauch2000Unter-7477,
  year={2000},
  title={Untersuchungen zur biologischen Rolle der Matrixmetalloproteinase MMP-19},
  author={Mauch, Simon},
  address={Konstanz},
  school={Universität Konstanz}
}

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Prüfungsdatum der Dissertation

September 1, 2000