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TGF-β 和 Notch 信号通路在纤维化发病机制中的复杂相互作用。

The Complex Interplay of TGF-β and Notch Signaling in the Pathogenesis of Fibrosis.

机构信息

Institute of Cytology, Russian Academy of Sciences, St-Petersburg 194064, Russia.

出版信息

Int J Mol Sci. 2024 Oct 8;25(19):10803. doi: 10.3390/ijms251910803.

Abstract

Fibrosis is a major medical challenge, as it leads to irreversible tissue remodeling and organ dysfunction. Its progression contributes significantly to morbidity and mortality worldwide, with limited therapeutic options available. Extensive research on the molecular mechanisms of fibrosis has revealed numerous factors and signaling pathways involved. However, the interactions between these pathways remain unclear. A comprehensive understanding of the entire signaling network that drives fibrosis is still missing. The TGF-β and Notch signaling pathways play a key role in fibrogenesis, and this review focuses on their functional interplay and molecular mechanisms. Studies have shown synergy between TGF-β and Notch cascades in fibrosis, but antagonistic interactions can also occur, especially in cardiac fibrosis. The molecular mechanisms of these interactions vary depending on the cell context. Understanding these complex and context-dependent interactions is crucial for developing effective strategies for treating fibrosis.

摘要

纤维化是一个主要的医学挑战,因为它会导致不可逆转的组织重塑和器官功能障碍。它的进展对全球的发病率和死亡率有重大影响,但现有的治疗选择有限。对纤维化的分子机制的广泛研究揭示了许多涉及的因素和信号通路。然而,这些途径之间的相互作用尚不清楚。对驱动纤维化的整个信号网络的全面理解仍然缺失。TGF-β和 Notch 信号通路在纤维化中起着关键作用,本综述重点关注它们的功能相互作用和分子机制。研究表明,TGF-β和 Notch 级联在纤维化中存在协同作用,但也会发生拮抗相互作用,尤其是在心脏纤维化中。这些相互作用的分子机制取决于细胞环境。理解这些复杂和上下文相关的相互作用对于开发治疗纤维化的有效策略至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92d7/11477142/7fc4da901d4e/ijms-25-10803-g001.jpg

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