Mechanistic target of rapamycin complex 1 signaling regulates cell proliferation, cell survival, and differentiation in regenerating zebrafish fins.
Mechanistic target of rapamycin complex 1 signaling regulates cell proliferation, cell survival, and differentiation in regenerating zebrafish fins.
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DOI：
10.1186/s12861-014-0042-9
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发表时间：
2014-12-06
影响因子：
--
通讯作者：
Kikuchi Y
中科院分区：
文献类型：
--
作者：
Hirose K;Shiomi T;Hozumi S;Kikuchi Y
雷帕霉素复合物 1 (mTORC1) 信号通路的机制靶点与多细胞过程的功能有关，包括细胞生长和代谢。尽管最近的报告表明许多信号通路，包括 Activin、Bmp、Fgf、sonic hedgehog、胰岛素样生长因子 (IGF)、Notch、视黄酸和 Wnt，与非哺乳动物脊椎动物再生（也称为外胚性再生）有关，但 mTORC1 的功能仍然未知。为了研究 mTORC1 信号通路在斑马鱼尾鳍中的作用，我们使用抗磷酸化 S6 激酶的抗体和特定抑制剂雷帕霉素检查了 mTORC1 信号通路的激活和功能。 mTORC1 信号在芽基形成之前在射线内和伤口表皮细胞的增殖细胞中以及在再生生长过程中在增殖芽基细胞、伤口表皮细胞和成骨细胞中被激活。在胚基形成之前，射线内和伤口表皮细胞的增殖受到抑制，但细胞死亡不受雷帕霉素抑制 mTORC1 信号的影响。此外，雷帕霉素治疗抑制芽基和伤口表皮细胞在芽基形成和再生生长过程中的增殖和存活，以及在再生生长过程中抑制成骨细胞增殖和分化。我们进一步确定，在鳍再生过程中，mTORC1 信号传导通过 IGF-1 受体/磷脂酰肌醇-3 激酶和 Wnt 通路进行调节。综上所述，我们的研究结果表明，mTORC1 信号在 IGF 和 Wnt 信号通路下游的各个鳍再生阶段调节射线内细胞、伤口表皮、芽基细胞和/或成骨细胞的增殖、存活和分化。本文的在线版本 (doi:10.1186/s12861-014-0042-9) 包含补充材料，可供授权用户使用。
The mechanistic target of rapamycin complex1 (mTORC1) signaling pathway has been implicated in functions of multicellular processes, including cell growth and metabolism. Although recent reports showed that many signaling pathways, including Activin, Bmp, Fgf, sonic hedgehog, Insulin-like growth factor (IGF), Notch, retinoic acid, and Wnt, are implicated in non-mammalian vertebrate regeneration, also known as epimorphic regeneration, mTORC1 function remains unknown. To investigate the role of mTORC1 signaling pathway in zebrafish caudal fin, we examined the activation and function of mTORC1 signaling using an antibody against phosphorylated S6 kinase and a specific inhibitor, rapamycin. mTORC1 signaling is activated in proliferative cells of intra-ray and wound epidermal cells before blastema formation, as well as in proliferative blastema cells, wound epidermal cells, and osteoblasts during regenerative outgrowth. Before blastema formation, proliferation of intra-ray and wound epidermal cells is suppressed, but cell death is not affected by mTORC1 signaling inhibition with rapamycin. Moreover, rapamycin treatment inhibits blastema and wound epidermal cell proliferation and survival during blastema formation and regenerative outgrowth, as well as osteoblast proliferation and differentiation during regenerative outgrowth. We further determined that mTORC1 signaling is regulated through IGF-1 receptor/phosphatidylinositol-3 kinase and Wnt pathways during fin regeneration. Taken together, our findings reveal that mTORC1 signaling regulates proliferation, survival, and differentiation of intra-ray cells, wound epidermis, blastema cells, and/or osteoblasts in various fin regeneration stages downstream of IGF and Wnt signaling pathways. The online version of this article (doi:10.1186/s12861-014-0042-9) contains supplementary material, which is available to authorized users.
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影响因子：
4.6
作者：
Gauron, Carole;Rampon, Christine;Bouzaffour, Mohamed;Ipendey, Eliane;Teillon, Jeremie;Volovitch, Michel;Vriz, Sophie
通讯作者：
Vriz, Sophie
影响因子：
11.8
作者：
Tanaka, Elly M.;Reddien, Peter W.
通讯作者：
Reddien, Peter W.
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
影响因子：
4.6
作者：
Grotek, Bartholomaeus;Wehner, Daniel;Weidinger, Gilbert
通讯作者：
Weidinger, Gilbert
影响因子：
14.8
作者：
Chen, Baozhi;Dodge, Michael E.;Tang, Wei;Lu, Jianming;Ma, Zhiqiang;Fan, Chih-Wei;Wei, Shuguang;Hao, Wayne;Kilgore, Jessica;Williams, Noelle S.;Roth, Michael G.;Amatruda, James F.;Chen, Chuo;Lum, Lawrence
通讯作者：
Lum, Lawrence