SPINK9 Stimulates Metalloprotease/EGFR-Dependent Keratinocyte Migration via Purinergic Receptor Activation

0434707 - ÚMG 2015 RIV US eng J - Journal Article
Sperrhacke, M. - Fischer, J. - Wu, Z.H. - Klunder, S. - Sedláček, Radislav - Schroeder, J.M. - Meyer-Hoffert, U. - Reiss, K.
SPINK9 Stimulates Metalloprotease/EGFR-Dependent Keratinocyte Migration via Purinergic Receptor Activation.
Journal of Investigative Dermatology. Roč. 134, č. 6 (2014), s. 1645-1654. ISSN 0022-202X. E-ISSN 1523-1747
R&D Projects: GA ČR GAP303/10/2044
Institutional support: RVO:68378050
Keywords : SPINK * ADAM * keratinocyte
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.216, year: 2014

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.
Permanent Link: http://hdl.handle.net/11104/0238695