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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F14%3A00434707%21RIV15-GA0-68378050
rdf:type
n14:Vysledek skos:Concept
dcterms:description
Serine protease inhibitors of the Kazal-type 9 (SPINK9) is a keratinocyte-derived cationic peptide that is found most abundantly in the upper layers of the palmar plantar epidermis. In vitro, the peptide displays the capacity to inhibit specifically kallikrein-related peptidase 5 (KLK5). Here, we report that cells expressing SPINK9 secrete the peptide constitutively. Recombinant SPINK9 (rSPINK9) provoked transactivation of the EGFR in human keratinocytes, resulting in efficient downstream triggering of cell migration. Transactivation occurred via functional upregulation of a disintegrin and metalloproteases (ADAMs), as evidenced by suppression with a metalloproteinase inhibitor and an EGFR-blocking antibody. SPINK9 preparations isolated from human skin also displayed EGFR-transactivating capacity. The classical purinergic receptor antagonists oxidized ATP and pyridoxalphosphate-6-azophenyl-2',4',-disulfonic acid effectively suppressed EGFR transactivation by rSPINK9, indicating that in analogy to what has recently been reported for the cationic antimicrobial peptides cathelicidin LL-37 and bee venom melittin, purinergic receptors have an essential bridging role in promoting the upregulation of ADAM function by the cationic peptide. SPINK9 could represent an example of how a cationic peptide may subserve multiple and interrelated functions that contribute to the maintenance of the physical and immunological barrier of the skin. Serine protease inhibitors of the Kazal-type 9 (SPINK9) is a keratinocyte-derived cationic peptide that is found most abundantly in the upper layers of the palmar plantar epidermis. In vitro, the peptide displays the capacity to inhibit specifically kallikrein-related peptidase 5 (KLK5). Here, we report that cells expressing SPINK9 secrete the peptide constitutively. Recombinant SPINK9 (rSPINK9) provoked transactivation of the EGFR in human keratinocytes, resulting in efficient downstream triggering of cell migration. Transactivation occurred via functional upregulation of a disintegrin and metalloproteases (ADAMs), as evidenced by suppression with a metalloproteinase inhibitor and an EGFR-blocking antibody. SPINK9 preparations isolated from human skin also displayed EGFR-transactivating capacity. The classical purinergic receptor antagonists oxidized ATP and pyridoxalphosphate-6-azophenyl-2',4',-disulfonic acid effectively suppressed EGFR transactivation by rSPINK9, indicating that in analogy to what has recently been reported for the cationic antimicrobial peptides cathelicidin LL-37 and bee venom melittin, purinergic receptors have an essential bridging role in promoting the upregulation of ADAM function by the cationic peptide. SPINK9 could represent an example of how a cationic peptide may subserve multiple and interrelated functions that contribute to the maintenance of the physical and immunological barrier of the skin.
dcterms:title
SPINK9 Stimulates Metalloprotease/EGFR-Dependent Keratinocyte Migration via Purinergic Receptor Activation SPINK9 Stimulates Metalloprotease/EGFR-Dependent Keratinocyte Migration via Purinergic Receptor Activation
skos:prefLabel
SPINK9 Stimulates Metalloprotease/EGFR-Dependent Keratinocyte Migration via Purinergic Receptor Activation SPINK9 Stimulates Metalloprotease/EGFR-Dependent Keratinocyte Migration via Purinergic Receptor Activation
skos:notation
RIV/68378050:_____/14:00434707!RIV15-GA0-68378050
n3:aktivita
n15:I n15:P
n3:aktivity
I, P(GAP303/10/2044)
n3:cisloPeriodika
6
n3:dodaniDat
n12:2015
n3:domaciTvurceVysledku
n16:5782694
n3:druhVysledku
n17:J
n3:duvernostUdaju
n6:S
n3:entitaPredkladatele
n9:predkladatel
n3:idSjednocenehoVysledku
46644
n3:idVysledku
RIV/68378050:_____/14:00434707
n3:jazykVysledku
n13:eng
n3:klicovaSlova
SPINK; ADAM; keratinocyte
n3:klicoveSlovo
n10:keratinocyte n10:SPINK n10:ADAM
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[F84DAA2119A3]
n3:nazevZdroje
Journal of Investigative Dermatology
n3:obor
n11:EB
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
8
n3:projekt
n18:GAP303%2F10%2F2044
n3:rokUplatneniVysledku
n12:2014
n3:svazekPeriodika
134
n3:tvurceVysledku
Meyer-Hoffert, U. Klunder, S. Sperrhacke, M. Reiss, K. Schroeder, J. M. Sedláček, Radislav Wu, Z. H. Fischer, J.
n3:wos
000336193700023
s:issn
0022-202X
s:numberOfPages
10
n4:doi
10.1038/jid.2014.23