Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology
2020; Elsevier BV; Volume: 295; Issue: 49 Linguagem: Inglês
10.1074/jbc.rev120.014391
ISSN1083-351X
AutoresCarolyn Chen, Renato V. Iozzo,
Tópico(s)Fibroblast Growth Factor Research
ResumoThe 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. 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. The extracellular matrix (ECM) consists of a three-dimensional structural scaffold of macromolecules that provides an extensive reservoir of complex signaling molecules, masterfully orchestrating a plethora of biological functions affecting surrounding cells and tissue (1Manou D. Caon I. Bouris P. Triantaphyllidou I.E. Giaroni C. Passi A. Karamanos N.K. Vigetti D. Theocharis A.D. The complex interplay between extracellular matrix and cells in tissues.Methods Mol. 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A key player in ECM biology, HA is a ubiquitously expressed and predominant GAG found in all tissues and body fluids, regulating a complex network of functions (40Garantziotis S. Savani R.C. Hyaluronan biology: a complex balancing act of structure, function, location and context.Matrix Biol. 2019; 78-79 (30802498): 1-1010.1016/j.matbio.2019.02.002Crossref PubMed Scopus (37) Google Scholar). Although sophisticated in action, HA intrinsically possesses a physical structure that is astonishingly simple, composed of linear repeating disaccharide units of GlcNAc and GlcUA linked by β-(1,3) and β-(1,4) glycosidic bonds (Fig. 1A) (40Garantziotis S. Savani R.C. Hyaluronan biology: a complex balancing act of structure, function, location and context.Matrix Biol. 2019; 78-79 (30802498): 1-1010.1016/j.matbio.2019.02.002Crossref PubMed Scopus (37) Google Scholar). It uniquely exists as the only nonsulfated GAG and does not covalently bind to a protein core. 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