Cysteine-rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling.
Cysteine-rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling.
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富含半胱氨酸的蛋白 61 通过雷帕霉素复合物 1 的哺乳动物靶标和经典 Wnt 信号传导调节间充质干细胞的脂肪细胞分化。
DOI：
10.1096/fj.201700830rr
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Wang Baoli
中科院分区：
文献类型：
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作者：
Yang Yongxu;Qi Qi;Wang Yi;Shi Yaru;Yang Weili;Cen Yunzhu;Zhu Endong;Li Xiaoxia;Chen Di;Wang Baoli
新出现的证据表明，富含半胱氨酸的蛋白61（CYR 61）在软骨细胞、成骨细胞和破骨细胞的分化和发育中发挥作用;然而，人们对其在脂肪形成中的作用知之甚少。目前的研究表明，Cyr 61的表达水平在原代培养的骨髓基质细胞和建立的间充质细胞系，C3 H10 T1/2，成脂处理后的改变。过表达Cyr 61抑制C3 H10 T1/2和原代骨髓基质细胞分化为成熟脂肪细胞。相反，内源性Cyr 61的抑制诱导C3 H10 T1/2和原代骨髓基质细胞完全分化。机制研究表明，敲低Cyr 61可抑制β-catenin的核转位，并降低β-catenin和转录因子7样2的核蛋白水平。此外，Cyr 61的沉默增加了C3 H10 T1/2细胞中磷酸化核糖体蛋白S6激酶B1、哺乳动物雷帕霉素靶蛋白、真核翻译起始因子4 E结合蛋白1和核糖体蛋白S6的蛋白水平，这些蛋白是哺乳动物雷帕霉素靶蛋白复合物1（mTORC 1）信号传导的主要成分。另外的研究表明，用雷帕霉素处理显著减弱了Cyr 61小干扰RNA（siRNA）转染诱导的脂肪细胞形成。此外，Cyr 61 siRNA在β-catenin过表达的背景下也失去了刺激脂肪细胞形成的能力。综上所述，我们的研究提供了CYR 61通过多种信号通路调节脂肪细胞分化的证据，这些信号通路至少涉及mTORC 1信号的失活和经典Wnt信号的激活。杨，Y.，齐，Q.王玉，施，Y.，杨伟，Cen，Y.，Zhu，E.，Li，X.，Chen，D.，中国农业科学院，Wang，B.富含半胱氨酸的蛋白61通过哺乳动物雷帕霉素复合物1靶蛋白和经典Wnt信号传导调控间充质干细胞向脂肪细胞分化。FASEB J. 32，3096-3107（2018）。www.fasebj.org
Emerging evidence suggests that cysteine‐rich protein 61 (CYR61) plays a role in the differentiation and development of chondrocytes, osteoblasts, and osteoclasts; however, little is known about its role in adipogenesis. The current study indicates that the expression level of Cyr61 was altered in primary cultured marrow stromal cells and the established mesenchymal cell line, C3H10T1/2, after adipogenic treatment. Overexpressing Cyr61 repressed C3H10T1/2 and primary marrow stromal cells to differentiate into mature adipocytes. Conversely, inhibition of endogenous Cyr61 induced C3H10T1/2 and primary marrow stromal cells to fully differentiate. Mechanism investigations reveal that knockdown of Cyr61 inhibited the nuclear translocation of β‐catenin and decreased nuclear protein levels of β‐catenin and transcription factor 7‐like 2. Moreover, the silencing of Cyr61 increased protein levels of phosphorylated ribosomal protein S6 kinase B1, mammalian target of rapamycin, eukaryotic translation initiation factor 4E‐binding protein 1, and ribosomal protein S6—the major components of mammalian target of rapamycin complex 1 (mTORC1) signaling—in C3H10T1/2 cells. Additional investigations demonstrated that treatment with rapamycin significantly attenuated adipocyte formation that was induced by Cyr61 small interfering RNA (siRNA) transfection. Moreover, Cyr61 siRNA also lost its ability to stimulate adipocyte formation under the background of β‐catenin overexpression. Taken together, our study provides evidence that CYR61 regulates adipocyte differentiationviamultiple signaling pathways that involve at least the inactivation of mTORC1 signaling and the activation of canonical Wnt signaling.—Yang, Y., Qi, Q., Wang, Y., Shi, Y., Yang, W., Cen, Y., Zhu, E., Li, X., Chen, D., Wang, B. Cysteine‐rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling. FASEB J. 32, 3096–3107 (2018). www.fasebj.org