Decorin causes autophagy in endothelial cells via Peg3

Abstract

Significance We identified a function for a member of the extracellular matrix in the regulation of autophagy. Decorin, a member of the small leucine-rich proteoglycan family and an established pan-receptor tyrosine kinase inhibitor, evokes endothelial cell autophagy and inhibits angiogenesis. This process is mediated by a high-affinity interaction with VEGFR2 which leads to increased levels of Peg3, a tumor-suppressor gene. We provide mechanistic evidence that Peg3 is required to maintain basal levels of Beclin 1, a major autophagic marker. These data provide a paradigmatic shift for other soluble matrix constituents to regulate autophagy.

Decorin Induces Mitophagy in Breast Carcinoma Cells via Peroxisome Proliferator-activated Receptor γ Coactivator-1α (PGC-1α) and Mitostatin

“…7I), as recently shown to occur for other transformed cell lines (73). After knockdown of Beclin 1 (cf.…”

Endorepellin Evokes Autophagy in Endothelial Cells

“…4, B and C). Importantly, rapamycin also evoked PEG3 mRNA by ϳ4800-fold in HUVEC (data not shown), thus reinforcing PEG3 as a master regulator of endothelial cell autophagy (73).…”

“…Peg3 Plays a Key Role in Endorepellin-evoked AutophagyWe have recently discovered that Peg3 acts as a master regulator of autophagy by recruiting Beclin 1 and LC3 upon decorin treatment, as well as canonical autophagy inducers such as rapamycin and nutrient deprivation (73). Thus, we investigated whether Peg3 would also play a crucial role in endorepellinmediated autophagy in endothelial cells.…”

“…Human umbilical vein endothelial cells (HUVEC) were from Lifeline Cell Technology and grown in basal media supplemented with VascuLife EnGS LifeFactors kit (Lifeline Cell Technology) and used within the first five passages. Porcine aortic endothelial cells (PAE) and their transgenic counterparts expressing either VEGFR2 or VEGFR2-GFP-LC3 were described previously (67,73). PAE cells were stably transfected with a human BECN1 promoter (74) luciferase reporter construct as described previously (73).…”

Novel approaches of pharmacological preconditioning: the role of biglycan and miRNAs

“…This is in line with recent publications demonstrating that small leucinerich proteoglycans induce autophagy in endothelial cells [102] and modulation of autophagy may play a role in cytoprotection [21,103,104]. More detailed events on regulation of necrosis, apoptosis and autophagy by rhBGNc, however, needs to be further explored in separate studies.…”