TGF-β1 autocrine signalling and enamel matrix components

Saeko Kobayashi-Kinoshita; Yasuo Yamakoshi; Kazuo Onuma; Ryuji Yamamoto; Yoshinobu Asada

doi:10.1038/srep33644

TGF-β1 autocrine signalling and enamel matrix components

Sci Rep. 2016 Sep 16:6:33644. doi: 10.1038/srep33644.

Authors

Saeko Kobayashi-Kinoshita¹, Yasuo Yamakoshi², Kazuo Onuma³, Ryuji Yamamoto², Yoshinobu Asada¹

Affiliations

¹ Department of Pediatric Dentistry, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
² Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
³ National Institute of Advanced Industrial Science &Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ameloblasts / metabolism
Amelogenin / isolation & purification
Amelogenin / metabolism
Animals
Autocrine Communication*
Dental Enamel / metabolism*
Dynamic Light Scattering
Enzyme Activation
Epithelium / metabolism
Fluorescence Resonance Energy Transfer
Gene Expression Regulation
Humans
Kallikreins / metabolism
Matrix Metalloproteinase 20 / metabolism
Protein Binding
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor, Transforming Growth Factor-beta Type I
Receptors, Transforming Growth Factor beta / genetics
Receptors, Transforming Growth Factor beta / metabolism
Sus scrofa
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / metabolism*

Substances

Amelogenin
RNA, Messenger
Receptors, Transforming Growth Factor beta
Transforming Growth Factor beta1
Protein Serine-Threonine Kinases
Receptor, Transforming Growth Factor-beta Type I
TGFBR1 protein, human
Kallikreins
kallikrein 4
Matrix Metalloproteinase 20