2019年5月21日 · Here, we showed that transforming growth factor-β 1 (TGF-β 1), the key pro-fibrotic cytokine implicated in multiple fibrotic conditions, increased the production of activating transcription factor 4 (ATF4), the transcriptional master regulator of amino acid metabolism, to supply glucose-derived glycine to meet the amino acid requirements ...

2023年9月4日 · mTORC1 是环境和激素信号的关键调节因子，当氨基酸、葡萄糖、胆固醇和核苷酸等营养物质丰富时，它会激活合成代谢过程并抑制分解代谢过程。 （DOI: 10.1016/j.devcel.2022.02.024） mTORC2主要作为磷酸肌醇3激酶 (PI3K)信号传导的效应子来调节细胞存活和细胞骨架形成，通过增强激活来响应胰岛素、胰岛素样生长因子1 (IGF-1)和瘦素对PI3K的激活AKT和胰岛素信号通路的其他下游效应子。 两个mTOR复合物通过它们的底物相 …

最近的研究表明，mTORC1还能促进生长和增殖细胞中DNA复制和核糖体生物发生所需的核苷酸的合成。 mTORC1增加ATF4依赖的MTHFD2的表达，MTHFD2是线粒体四氢叶酸循环的关键组成部分，为嘌呤的合成提供一个碳单位。

2019年1月2日 · Here we demonstrate that rapamycin-insensitive mTORC1 signaling via 4E-BP1 is a critical pathway for TGF-β1 stimulated collagen synthesis in human lung fibroblasts, whereas canonical PI3K/Akt...

2019年5月21日 · Our findings suggest that targeting the TGF-β 1 –mTORC1–ATF4 axis may represent a novel therapeutic strategy for interfering with myofibroblast function in fibrosis and potentially in other conditions, including cancer.

2024年2月29日 · We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-β, and was enhanced in TRAF2 -/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1.

In this study, we examined whether intravitreal injection of TGF-β1 into the mouse eye elicits senescence-like morphological alterations in the RPE and if this can be prevented by suppressing mammalian target of rapamycin complex 1 (mTORC1) or NADPH oxidase (NOX) signaling.

2021年8月10日 · Our study identifies TGF-β-mediated mTORC1 inhibition in early Tpex cells as one of the key pathways that preserve mitochondrial function and OXPHOS. Our analyses indicate that the tight regulation of mTOR is central to the metabolic properties of Tpex and Tex cells. mTOR is a major metabolic hub that senses intracellular and extracellular ...

2024年10月14日 · The cardinal pro-fibrotic mediator TGF-β1 has been widely implicated in promoting fibrogenesis and is a potent inducer of CTHRC1 and COL1A1 expression. In addition to the canonical Smad signalling pathway, TGF-β1-induced collagen I production is under critical regulatory control by the mTORC1/4E-BP1 signalling hub.

2024年7月1日 · In this study, we evaluated the effects of CZ415, a pan-mTOR inhibitor that could effectively block both mTORC1/4E-BP1 and mTORC2 pathways, aiming to counteract TGF-β1-induced fibrosis in human Tenon's fibroblasts (HTFs) in vitro, and in a rat model of glaucoma filtering surgery.