Nephronectin plays critical roles in Sox2 expression and proliferation in dental epithelial stem cells via EGF-like repeat domains

被引：29

作者：

Arai, Chieko ^{[1
]}

Yoshizaki, Keigo ^{[1
]}

Miyazaki, Kanako ^{[1
]}

Saito, Kan ^{[2
]}

Yamada, Aya ^{[2
]}

Han, Xue ^{[1
]}

Funada, Keita ^{[1
]}

Fukumoto, Emiko ^{[2
]}

Haruyama, Naoto ^{[1
]}

Iwamoto, Tsutomu ^{[3
]}

Takahashi, Ichiro ^{[1
]}

Fukumoto, Satoshi ^{[2
]}

机构：

[1] Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth Dev, Sect Orthodont & Dentofacial Orthoped, Fukuoka 8128582, Japan

[2] Tohoku Univ Grad Sch Dent, Dept Oral Hlth & Dev Sci, Div Pediat Dent, Sendai, Miyagi 9808575, Japan

[3] Tokushima Univ Grad Sch, Inst Biomed Sci, Dept Pediat Dent, Tokushima 7708540, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

日本学术振兴会;

关键词：

GROWTH-FACTOR RECEPTOR; SELF-RENEWAL; PROTEIN NEPHRONECTIN; TISSUE INTERACTIONS; TOOTH; CRYPTOPHTHALMOS; ORGANIZATION; LINEAGES; PATHWAY;

D O I：

10.1038/srep45181

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tooth development is initiated by epithelial-mesenchymal interactions via basement membrane (BM) and growth factors. In the present study, we found that nephronectin (Npnt), a component of the BM, is highly expressed in the developing tooth. Npnt localizes in the BM on the buccal side of the tooth germ and shows an expression pattern opposite that of the dental epithelial stem cell marker Sox2. To identify the roles of Npnt during tooth development, we performed knockdown and overexpression experiments using ex vivo organ and dental epithelial cell cultures. Our findings showed that loss of Npnt induced ectopic Sox2-positive cells and reduced tooth germ size. Over expression of Npnt showed increased proliferation, whereas the number of Sox2-positive cells was decreased in dental epithelial cells. Npnt contains 5 EGF-like repeat domains, as well as an RGD sequence and MAM domain. We found that the EGF-like repeats are critical for Sox2 expression and cell proliferation. Furthermore, Npnt activated the EGF receptor (EGFR) via the EGF-like repeat domains and induced the PI3K-Akt signaling pathway. Our results indicate that Npnt plays a critical scaffold role in dental epithelial stem cell differentiation and proliferation, and regulates Sox2 expression during tooth development.

引用

页数：12

共 43 条

[1] Context-Dependent Wiring of Sox2 Regulatory Networks for Self-Renewal of Embryonic and Trophoblast Stem Cells [J].