title: Interleukin-1β-induced autophagy-related gene 5 regulates proliferation of embryonic stem cell-derived odontoblastic cells.
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.
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozeki
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hase
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Hiyama
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kawai
authors.affiliation: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, 464-8650, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi, 464-8651, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, 464-8650, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Mogi
mesh_terms: D000818:Animals; D000071187:Autophagy-Related Protein 5; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009804:Odontoblasts / Q000166:cytology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C495773:Atg5 protein, mouse; C545865:Atg5 protein, rat; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D019278:Matrix Metalloproteinase 3