Inhibition of hair follicle growth by a laminin-1 G-domain peptide, RKRLQVQLSIRT, in an organ culture of isolated vibrissa rudiment.
We established a serum-free organ culture system of isolated single vibrissa rudiments taken from embryonic day 13 mice. This system allowed us to test more than 30 laminin-derived cell adhesive peptides to determine their roles on the growth and differentiation of vibrissa hair follicles. We found that the RKRLQVQLSIRT sequence (designated AG-73), which mapped to the LG-4 module of the laminin-alpha1 chain carboxyl-terminal G domain, perturbed the growth of hair follicles in vitro. AG-73 is one of the cell-binding peptides identified from more than 600 systematically synthesized 12 amino acid peptides covering the whole amino acid sequence of the laminin-alpha1, -beta1, and -gamma1 chains, by cell adhesion assay. Other cell-adhesive laminin peptides and a control scrambled peptide, LQQRRSVLRTKI, however, failed to show any significant effects on the growth of hair follicles. The AG-73 peptide binds to syndecan-1, a transmembrane heparan-sulfate proteoglycan. Syndecan-1 was expressed in both the mesenchymal condensation and the epithelial hair peg of developing vibrissa, suggesting that AG-73 binding to the cell surface syndecan-1 perturbed the epithelial-mesenchymal interactions of developing vibrissa. The formation of hair bulbs was aberrant in the explants treated with AG-73. In addition, impaired basement membrane formation, an abnormal cytoplasmic bleb formation, and an unusual basal formation of actin bundles were noted in the AG-73-treated-hair matrix epithelium, indicating that AG-73 binding perturbs various steps of epithelial morphogenesis, including the basement membrane remodeling. We also found a region-specific loss of the laminin-alpha1 chain in the basement membrane at the distal region of the invading hair follicle epithelium, indicating that laminins play a part in hair morphogenesis.
Hayashi
Kazuhiro
K
Department of Plastic and Reconstructive Surgery, Kitasato University School of Medicine, Kitasato, Sagamihara, Japan.
Mochizuki
Mayumi
M
Nomizu
Motoyoshi
M
Uchinuma
Eijyu
E
Yamashina
Shohei
S
Kadoya
Yuichi
Y
D000818:Animals; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005333:Fetus / Q000187:drug effects; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008813:Mice, Inbred ICR; D016253:Microscopy, Immunoelectron; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis; D053668:Syndecan-1; D053667:Syndecans; D014738:Vibrissae / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*
C105786:AG 73; D007797:Laminin; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; C121346:laminin 1; C084098:laminin A