title: TGF-β1 autocrine signalling and enamel matrix components.
abstract: Transforming growth factor-β1 (TGF-β1) is present in porcine enamel extracts and is critical for proper mineralization of tooth enamel. Here, we show that the mRNA of latent TGF-β1 is expressed throughout amelogenesis. Latent TGF-β1 is activated by matrix metalloproteinase 20 (MMP20), coinciding with amelogenin processing by the same proteinase. Activated TGF-β1 binds to the major amelogenin cleavage products, particularly the neutral-soluble P103 amelogenin, to maintain its activity. The P103 amelogenin-TGF-β1 complex binds to TGFBR1 to induce TGF-β1 signalling. The P103 amelogenin-TGF-β1 complex is slowly cleaved by kallikrein 4 (KLK4), which is secreted into the transition- and maturation-stage enamel matrix, thereby reducing TGF-β1 activity. To exert the multiple biological functions of TGF-β1 for amelogenesis, we propose that TGF-β1 is activated or inactivated by MMP20 or KLK4 and that the amelogenin cleavage product is necessary for the in-solution mobility of TGF-β1, which is necessary for binding to its receptor on ameloblasts and retention of its activity.
authors.affiliation: Department of Pediatric Dentistry, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Kobayashi-Kinoshita
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamakoshi
authors.affiliation: National Institute of Advanced Industrial Science &Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Onuma
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatric Dentistry, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Asada
mesh_terms: D000565:Ameloblasts / Q000378:metabolism; D053523:Amelogenin / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication; D003743:Dental Enamel / Q000378:metabolism*; D000067493:Dynamic Light Scattering; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D053519:Matrix Metalloproteinase 20 / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D034421:Sus scrofa; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053523:Amelogenin; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; D007610:Kallikreins; C120801:kallikrein 4; D053519:Matrix Metalloproteinase 20