Multiple pathways promote microtubule stabilization in senescent intestinal epithelial cells.

Siwei Chu, Ossama Moujaber, Serge Lemay, Ursula Stochaj
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引用次数: 2

Abstract

Intestinal epithelial cells are critical for gastrointestinal homeostasis. However, their function declines during aging. The aging-related loss of organ performance is largely driven by the increase in senescent cells. To date, the hallmarks and molecular mechanisms related to cellular senescence are not fully understood. Microtubules control epithelial functions, and we identified microtubule stabilization as a phenotypic marker of senescent intestinal epithelial cells. The senescence inducer determined the pathway to microtubule stabilization. Specifically, enhanced microtubule stability was associated with α-tubulin hyperacetylation or increased abundance of the microtubule-binding protein tau. We show further that overexpression of MAPT, which encodes tau, augmented microtubule stability in intestinal epithelial cells. Notably, pharmacological microtubule stabilization was sufficient to induce cellular senescence. Taken together, this study provides new insights into the molecular mechanisms that control epithelial cell homeostasis. Our results support the concept that microtubule stability serves as a critical cue to trigger intestinal epithelial cell senescence.

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多种途径促进衰老肠上皮细胞的微管稳定。
肠上皮细胞对胃肠道稳态至关重要。然而,它们的功能随着年龄的增长而下降。与衰老相关的器官功能丧失主要是由衰老细胞的增加引起的。迄今为止,与细胞衰老有关的标志和分子机制尚未完全了解。微管控制上皮细胞的功能,我们发现微管稳定是衰老肠上皮细胞的表型标记。衰老诱导剂确定了微管稳定的途径。具体来说,微管稳定性的增强与α-微管蛋白超乙酰化或微管结合蛋白tau丰度的增加有关。我们进一步证明,编码tau蛋白的MAPT过表达增强了肠上皮细胞的微管稳定性。值得注意的是,药理微管稳定足以诱导细胞衰老。综上所述,本研究为控制上皮细胞稳态的分子机制提供了新的见解。我们的研究结果支持了微管稳定性作为触发肠上皮细胞衰老的关键线索的概念。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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