TGF-?1 autocrine signalling and enamel matrix components.

ABSTRACT: Transforming growth factor-?1 (TGF-?1) is present in porcine enamel extracts and is critical for proper mineralization of tooth enamel. Here, we show that the mRNA of latent TGF-?1 is expressed throughout amelogenesis. Latent TGF-?1 is activated by matrix metalloproteinase 20 (MMP20), coinciding with amelogenin processing by the same proteinase. Activated TGF-?1 binds to the major amelogenin cleavage products, particularly the neutral-soluble P103 amelogenin, to maintain its activity. The P103 amelogenin-TGF-?1 complex binds to TGFBR1 to induce TGF-?1 signalling. The P103 amelogenin-TGF-?1 complex is slowly cleaved by kallikrein 4 (KLK4), which is secreted into the transition- and maturation-stage enamel matrix, thereby reducing TGF-?1 activity. To exert the multiple biological functions of TGF-?1 for amelogenesis, we propose that TGF-?1 is activated or inactivated by MMP20 or KLK4 and that the amelogenin cleavage product is necessary for the in-solution mobility of TGF-?1, which is necessary for binding to its receptor on ameloblasts and retention of its activity.

SUBMITTER: Kobayashi-Kinoshita S 

PROVIDER: S-EPMC5025654 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature