RRC ID 37028
Author Ozeki N, Hase N, Hiyama T, Yamaguchi H, Kawai R, Kondo A, Matsumoto T, Nakata K, Mogi M.
Title Interleukin-1β-induced autophagy-related gene 5 regulates proliferation of embryonic stem cell-derived odontoblastic cells.
Journal 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.
Volume 10(4)
Pages e0124542
Published 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
Times Cited 7
Human and Animal Cells B6G-2(AES0003)