The extracellular matrix encompasses a reservoir of bioactive macromolecules that modulates a cornucopia of biological functions. A prominent body of work posits matrix constituents as master regulators of autophagy and angiogenesis and provides molecular insight into how these two processes are coordinated. Here, we review current understanding of the molecular mechanisms underlying hyaluronan and HAS2 regulation and the role of soluble proteoglycan in affecting autophagy and angiogenesis. Specifically, we assess the role of proteoglycan-evoked autophagy in regulating angiogenesis via the HAS2-hyaluronan axis and ATG9A, a novel HAS2 binding partner. We discuss extracellular hyaluronan biology and the post-transcriptional and post-translational modifications that regulate its main synthesizer, HAS2. We highlight the emerging group of proteoglycans that utilize outside-in signaling to modulate autophagy and angiogenesis in cancer microenvironments and thoroughly review the most up-to-date understanding of endorepellin signaling in vascular endothelia, providing insight into the temporal complexities involved.

中文翻译：

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来自基质的血管抑制线索：内皮细胞自噬与透明质酸生物学的结合


细胞外基质包含调节生物功能的生物活性大分子的储存库。一项重要的工作将基质成分视为自噬和血管生成的主要调节因子，并提供了如何协调这两个过程的分子见解。在此，我们回顾了目前对透明质酸和 HAS2 调节分子机制以及可溶性蛋白聚糖在影响自噬和血管生成中的作用的理解。具体来说，我们评估了蛋白聚糖诱发的自噬在通过 HAS2-透明质酸轴和 ATG9A（一种新型 HAS2 结合伴侣）调节血管生成中的作用。我们讨论细胞外透明质酸生物学以及调节其主要合成器 HAS2 的转录后和翻译后修饰。我们重点介绍了一组新兴的蛋白聚糖，它们利用由外向内的信号传导来调节癌症微环境中的自噬和血管生成，并彻底回顾了对血管内皮细胞内皮素信号传导的最新理解，从而深入了解所涉及的时间复杂性。