RRC ID |
37028
|
著者 |
Ozeki N, Hase N, Hiyama T, Yamaguchi H, Kawai R, Kondo A, Matsumoto T, Nakata K, Mogi M.
|
タイトル |
Interleukin-1β-induced autophagy-related gene 5 regulates proliferation of embryonic stem cell-derived odontoblastic cells.
|
ジャーナル |
PLoS One
|
Abstract |
We previously established a method for the differentiation of induced pluripotent stem cells and embryonic stem cells into α2 integrin-positive odontoblast-like cells. We also reported that Wnt5 in response to interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation in these cells. Our findings suggest that MMP-3 plays a potentially unique physiological role in the generation of odontoblast-like cells under an inflammatory state. Here, we examined whether up-regulation of autophagy-related gene (Atg) 5 by IL-1β was mediated by Wnt5 signaling, thus leading to increased proliferation of odontoblast-like cells. IL-1β increased the mRNA and protein levels of Atg5, microtubule-associated protein 1 light chain (LC3, a mammalian homolog of yeast Atg8) and Atg12. Treatment with siRNAs against Atg5, but not LC3 and Atg12, suppressed the IL-1β-induced increase in MMP-3 expression and cell proliferation. Our siRNA analyses combined with western blot analysis revealed a unique sequential cascade involving Atg5, Wnt5a and MMP-3, which resulted in the potent increase in odontoblastic cell proliferation. These results demonstrate the unique involvement of Atg5 in IL-1β-induced proliferation of embryonic stem cell-derived odontoblast-like cells.
|
巻・号 |
10(4)
|
ページ |
e0124542
|
公開日 |
2015-1-1
|
DOI |
10.1371/journal.pone.0124542
|
PII |
PONE-D-14-54544
|
PMID |
25894570
|
PMC |
PMC4403923
|
MeSH |
Animals
Autophagy-Related Protein 5
Cell Differentiation / drug effects
Cell Line
Cell Proliferation / drug effects
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / drug effects*
Embryonic Stem Cells / metabolism
Gene Expression Regulation, Enzymologic / drug effects
Gene Silencing
Matrix Metalloproteinase 3 / metabolism
Mice
Microtubule-Associated Proteins / deficiency
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
Odontoblasts / cytology*
Proteins / genetics
Proteins / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / genetics
Rats
Signal Transduction / drug effects
Wnt Proteins / genetics
Wnt Proteins / metabolism
|
IF |
2.74
|
引用数 |
7
|
WOS 分野
|
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
B6G-2(AES0003) |