Laminin alpha3 LG4 module induces keratinocyte migration: involvement of matrix metalloproteinase-9.
Laminin alpha3 chain, a functionally key subunit of laminin-5, contains a large globular module (G module) which consists of a tandem repeat of five homologous LG modules (LG1-5). We previously demonstrated that the LG4 module of laminin alpha3 chain (alpha3 LG4) induces a matrix metalloproteinase-1 (MMP-1) expression through the interaction with syndecans leading to MAPK activation/IL-1beta expression signaling loop (Utani et al., J. Biol. Chem. 278, 34483-34490, 2003). Here, we show that a recombinant alpha3 LG4 and synthetic peptides containing syndecan binding motif induced a cell motility and a MMP-9 expression in ketarinocytes. The synthetic peptide (A3G756)-induced cell migration and MMP-9 upregulation were inhibited by each application of a heparin and an IL-1 receptor antagonist (IL-1RA), suggesting the involvement of syndecans and IL-1beta autocrine. Furthermore, the A3G756-induced cell motility was inhibited by an MMP-9 inhibitor and a neutralizing antibody of MMP-9, indicating induced cell motility was dependent on an MMP-9 activity. Taken these together, laminin-5 alpha3 LG4 module may play an important role in re-epithelialization at tissue remodeling.
Momota
Yutaka
Y
Department of Dermatology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Suzuki
Nobuharu
N
Kasuya
Yoshitoshi
Y
Kobayashi
Takashi
T
Mizoguchi
Masako
M
Yokoyama
Fumiharu
F
Nomizu
Motoyoshi
M
Shinkai
Hiroshi
H
Iwasaki
Toshiroh
T
Utani
Atsushi
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology*; D007797:Laminin / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D053667:Syndecans; D020080:Tandem Repeat Sequences
D018076:DNA, Complementary; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007797:Laminin; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D053667:Syndecans; C095567:laminin alpha 3; D020780:Matrix Metalloproteinase 9