56 research outputs found
Let It Flow: Morpholino Knockdown in Zebrafish Embryos Reveals a Pro-Angiogenic Effect of the Metalloprotease Meprin α2
BACKGROUND: Meprin metalloproteases are thought to be involved in basic physiological functions such as cell proliferation and tissue differentiation. However, the specific functions of these enzymes are still ambiguous, although a variety of growth factors and structural proteins have been identified as meprin substrates. The discovery of meprins alpha(1), alpha(2) and beta in teleost fish provided the basis for uncovering their physiological functions by gene silencing in vivo. METHODOLOGY/PRINCIPAL FINDINGS: A Morpholino knockdown in zebrafish embryos targeting meprin alpha(1) and beta mRNA caused defects in general tissue differentiation. But meprin alpha(2) morphants were affected more specifically and showed severe failures in the formation of the vascular system provoking the hypothesis of a pro-angiogenic effect. The blood circulation was largely diminished resulting in erythrocyte accumulation. These phenotypes mimic a previously described VEGF-A morphant, revealing a possible role of meprin alpha in VEGF-A activation. Indeed, human recombinant meprin alpha processed the vascular endothelial growth factor-A (VEGF-A) specifically, revealing the same cleavage products detectable for VEGF from zebrafish whole lysate. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Thus, we conclude that meprins play a significant role in VEGF-A processing, subsequently regulating angiogenesis. Therefore, meprin alpha might be a new therapeutic target in cardiovascular diseases or in tumor growth inhibition
The GALAD Score as Potential Screening Test for Hepatocellular Carcinoma in Nonalcoholic Steatohepatitis: An International Multicenter Study
EXTRAKTIVE AUFARBEITUNG VON INTRAZELLULAREN ENZYMEN
Wäßrige Phasensysteme weisen einen hohen Wassergehalt auf, der sie fiir die Verteilung
von Biopolymeren geeignet macht. Durch selektive Extraktion in solchen Systemen
wurden bereits zahlreiche intrazelluläre Enzyme, z. T. auch im technischen
Maßstab, aufgearbeitet. In diesem Artikel wird eine kurze Übersicht über die
Grundlagen und den Entwicklungsstand der Technologie gegeben
Direct Gas-Phase Epoxidation of Propene with Hydrogen Peroxide on TS-1 Zeolite in a Microstructured Reactor
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