ヤマムラ　マサヒロ   Masahiro Yamamura   山村　真弘    所属   川崎医科大学  医学部    職種   学長付講師
言語種別	英語
発表タイトル	Wnt signaling during transition from cell proliferation to differentiation in myoblast cells.
会議名	WNT2011
学会区分	国際学会及び海外の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎Tanaka Shingo, Nishimatsu Shin-ichiro, Yamamura Masahiro, Nohno Tsutomu
発表年月日	2011/07/01
開催地 （都市, 国名）	LA, USA
学会抄録	WNT2011 Abstract Book 25
概要	Wnt3a and beta-catenin are required to induce transcription of muscle-specific genes in embryonic carcinoma cells, also cause satellite-cell proliferation during adult skeletal muscle regeneration. beta-Catenin forms a complex with TCF/Lef-1, and eventually induces expression of the cyclin D1 and c-myc genes, although expression of these genes is suppressed during differentiation of the myoblast cells. Using C2C12 cells, we examined the transcriptional change in signaling components in Wnt pathways during myoblast proliferation and differentiation. We found that Wnt9a, Sfrp2 and porcupine expressions are significantly elevated in the differentiating C2C12 cells. Overexpression of Wnt3a induced less troponin T-positive myotubes than that of Wnt4 and Wnt5a. Wnt3a-induced TOFFLASH activity was reduced by co-expression with Wnt4, suggesting that Wnt3a promotes the myoblast proliferation whereas Wnt4 stimulates the differentiation. C2C12 cell proliferation and motility were also reduced by Wnt4 expression. A small-molecule inhibitor of beta-catenin/Tcf complex formation, FH535, reduced basal beta- catenin protein and decreased the cell proliferation. K252a, a protein kinase inhibitor, increased membrane-bound beta-catenin and enhanced the myoblast fusion. These results suggest that different Wnt ligands control subcellular localization of beta-catenin and manage the myoblast proliferation and myotube formation. beta-Catenin is acting as a molecular switch regulating the transition from cell proliferation to myogenic differentiation.