SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via purinergic receptor activation.

  title={SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via purinergic receptor activation.},
  author={Maria Sperrhacke and J. Fischer and Zhihong Wu and Sarah Kl{\"u}nder and R. Sedl{\'a}{\vc}ek and J. Schroeder and U. Meyer-Hoffert and K. Reiss},
  journal={The Journal of investigative dermatology},
  volume={134 6},
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… Expand
Skin-Derived SPINK9 Kills Escherichia coli.
SPINK9 is a member of epidermal antimicrobial peptides for selective killing of E. coli, which might contribute to the innate barrier function of human skin. Expand
Desmoglein 3-Dependent Signaling Regulates Keratinocyte Migration and Wound Healing.
It is shown that levels of active p38MAPK associated with Dsc3 are increased in Dsg3-deficient cells, indicating that Dsg 3 controls a switch from an adhesive to a migratory keratinocyte phenotype via p38 MAPK inhibition, which may foster wound closure by allowing p38MapK-dependent migration. Expand
Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune responses in skin cells and promote keratinocyte migration
Pep19-2.5 and the structurally related compound Pep19-4LF are investigated for their therapeutic application in bacterial skin infections and suggest a novel therapeutic target for the treatment of patients with acute and chronic skin infections. Expand
Kallikreins - The melting pot of activity and function.
The current state of knowledge regarding the physiological functions of KLKs in major human organs is presented and recent discoveries pertinent to the involvement of kallikreins in cell signaling and in viral infections are outlined. Expand
Investigations on the activity of synthetic anti-lipopolysaccharide peptidesagainst cytoplasmic lipopolysaccharide-induced responses and their anti-inflammatory and wound healing-promoting effect in the skin
This work aimed to investigate whether Pep19-2.5 is able to suppress cytoplasmic LPS-induced inflammation under more physiological conditions by using OMVs which naturally transfer LPS to the cytosol. Expand
Antimicrobial endotoxin‐neutralizing peptides promote keratinocyte migration via P2X7 receptor activation and accelerate wound healing in vivo
This work investigated the mechanism of peptide‐induced cell migration and if Pep19‐2.5 accelerates wound closure in vivo and found that the antimicrobial endotoxin‐neutralizing peptide Pep19.5 promotes artificial woundclosure in keratinocytes. Expand
Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential.
The results show that LL37-Au NPs have the capacity to prolong the phosphorylation of EGFR and ERK1/2 and enhance the migratory properties of keratinocytes in a large in vitro wound model and in vivo, and the conjugation of AMPs to NPs offers a promising platform to enhance their pro-regenerative properties. Expand
Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds
Evaluated AMPs for the treatment of bacterial SSTIs and wounds and an overview of the mechanisms of actions of AMPs that contribute to combat skin infections and to improve wound healing, as well as highlighting perspectives for future therapies and which issues remain. Expand
Saliva induces expression of antimicrobial peptides and promotes intracellular killing of bacteria in keratinocytes by epidermal growth factor receptor transactivation
Saliva promotes wound healing and plays a role in keeping the wound free of infection during licking of skin wounds, according to the World Health Organization. Expand
Topical antimicrobial peptide formulations for wound healing: Current developments and future prospects.
An overview is provided of the AMPs and current understanding of their formulations for topical wound healing applications along with suitable examples and future prospects for the development of effective combination AMP formulations are discussed. Expand


Identification of Lympho-Epithelial Kazal-Type Inhibitor 2 in Human Skin as a Kallikrein-Related Peptidase 5-Specific Protease Inhibitor
It is suggested that LEKTI-2 contributes to the regulation of the desquamation process in human skin by specifically inhibiting KLK5. Expand
SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor.
A possible role for SPINK9 is suggested in the site-specific epidermal differentiation of palms and soles in skin desquamation as an initiating activating enzyme in proteolytic cascades formed by KLKs. Expand
Characterization of SPINK9, a KLK5-specific inhibitor expressed in palmo-plantar epidermis
Modeling of the enzyme-inhibitor complexes showed that the reactive loop of SPINK9 fits very well into the deep negatively charged binding pocket of KLK5 and substitution with a positively charged amino acid at position 48 resulted in a more efficient inhibitor at higher pH. Expand
P2Y2 Nucleotide Receptors Mediate Metalloprotease-dependent Phosphorylation of Epidermal Growth Factor Receptor and ErbB3 in Human Salivary Gland Cells
It is demonstrated that in human salivary gland (HSG) cells, activation of the P2Y2R by its agonist induces phosphorylation of ERK1/2 via two distinct mechanisms, a rapid, protein kinase C-dependent pathway and a slower and prolonged, epidermal growth factor receptor (EGFR)-dependent pathway. Expand
Melittin Modulates Keratinocyte Function through P2 Receptor-dependent ADAM Activation*
It is reported that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Expand
Metalloproteinase-mediated, context-dependent function of amphiregulin and HB-EGF in human keratinocytes and skin.
Data show that distinct EGFR ligands stimulate KC behavior in different cellular contexts, and in an MP-dependent fashion, similar to that of autocrine KC proliferation and ERK phosphorylation. Expand
Serine Protease Inhibitor Kazal Type 1 Promotes Proliferation of Pancreatic Cancer Cells through the Epidermal Growth Factor Receptor
Analysis of the expression of SPINK1 and EGFR in pancreatic tubular adenocarcinomas and pancreatic intraepithelial neoplasm and the effect of inhibitors suggest that SPink1 stimulates the proliferation of pancreatic cancer cells through the EGFR/mitogen-activated protein kinase cascade. Expand
Kallikrein‐mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin
  • K. Yamasaki, J. Schauber, +7 authors R. Gallo
  • Biology, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2006
Observations demonstrate that the balance of proteolytic activity at an epithelial interface will control innate immune defense and regulate the antimicrobial effects of cathelicidins in skin. Expand
A Novel P2X7 Receptor Activator, the Human Cathelicidin-Derived Peptide LL37, Induces IL-1β Processing and Release1
It is reported that LL37 stimulation of LPS-primed monocytes leads to maturation and release of IL-1β via the P2X7 receptor, and it is concluded that endogenous LL37 may promote IL- 1β processing and release via direct activation of P2 X7 receptors. Expand
Induction of Keratinocyte Migration via Transactivation of the Epidermal Growth Factor Receptor by the Antimicrobial Peptide LL-371
It is suggested that LL-37 closes skin wounds by the induction of keratinocyte migration via heparin-binding-EGF-mediated transactivation of EGFR, and SOCS1/Jak2 binding protein or SOCS3/CIS3 negatively regulate this migration. Expand