Institute of Pharmacology and Toxicology, Goethe University, Frankfurt, Germany.
Institute of Biochemistry II, School of Medicine, Goethe University, Frankfurt, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt, Germany.
Matrix Biol. 2021 Jun;100-101:1-8. doi: 10.1016/j.matbio.2021.06.002. Epub 2021 Jul 2.
In recent years, extensive research has uncovered crucial regulatory roles for the extracellular matrix (ECM) in regulating autophagy. Autophagy is a ubiquitous and highly conserved catabolic process that allows the selective removal and recycling of cytosolic components via lysosomal or vacuolar degradation. Due to its pivotal role in cellular homeostasis, the impairment of autophagy is involved in the pathophysiology of numerous diseases, comprising infectious diseases, immune and neurodegenerative disorders, renal and hepatic diseases, intervertebral and cartilage disorders, as well as fibrosis and cancer. Several ECM-derived proteoglycans and proteins, including decorin, biglycan, endorepellin, endostatin, collagen VI, and plasminogen kringle 5, have been identified as strong inducers of autophagy. In contrast, laminin α2, perlecan, and lumican exert opposite function by suppressing autophagy. Importantly, by direct interaction with various receptors, which interplay with their co-receptors and adhesion molecules, the ECM is able to direct autophagy in a molecular and cell context-specific manner. Thus, vast pharmacological potential resides in translating this knowledge into the development of ECM-derived therapeutics selectively regulating autophagy.
近年来，大量研究揭示了细胞外基质（ECM）在调节自噬方面的关键调节作用。自噬是一种普遍存在且高度保守的分解代谢过程，通过溶酶体或液泡降解来选择性地去除和回收细胞质成分。由于自噬在细胞稳态中起着关键作用，自噬的损伤与许多疾病的病理生理学有关，包括传染病、免疫和神经退行性疾病、肾脏和肝脏疾病、椎间盘和软骨疾病以及纤维化和癌症。几种 ECM 衍生的蛋白聚糖和蛋白质，包括饰胶蛋白聚糖、大软骨素蛋白聚糖、内皮抑制素、内皮抑素、胶原 VI 和纤溶酶原kringle 5，已被确定为自噬的强诱导剂。相比之下，层粘连蛋白α2、perlecan 和 lumican 通过抑制自噬发挥相反的作用。重要的是，通过与各种受体的直接相互作用，这些受体与它们的共受体和粘附分子相互作用，ECM 能够以分子和细胞上下文特异性的方式指导自噬。因此，将这些知识转化为开发选择性调节自噬的 ECM 衍生治疗方法具有巨大的药理学潜力。
