Stimulatory effects of advanced glycation endproducts (AGEs) on fibronectin matrix assembly. Author Alexandra Pastino, Todd Greco, Rommel Mathias, Ileana Cristea, Jean Schwarzbauer Publication Year 2017 Type Journal Article Abstract Advanced glycation endproducts (AGEs) are a heterogeneous group of compounds that form via non-enzymatic glycation of proteins throughout our lifespan and at a higher rate in certain chronic diseases such as diabetes. AGEs contribute to the progression of fibrosis, in part by stimulating cellular pathways that affect gene expression. Long-lived ECM proteins are targets for non-enzymatic glycation but the question of whether the AGE-modified ECM leads to excess ECM accumulation and fibrosis remains unanswered. In this study, cellular changes due to AGE accretion in the ECM were investigated. Non-enzymatic glycation of proteins in a decellularized fibroblast ECM was achieved by incubating the ECM in a solution of methylglyoxal (MGO). Mass spectrometry of fibronectin (FN) isolated from the glycated matrix identified twenty-eight previously unidentified MGO-derived AGE modification sites including functional sites such as the RGD integrin-binding sequence. Mesangial cells grown on the glycated, decellularized matrix assembled increased amounts of FN matrix. Soluble AGE-modified bovine serum albumin (BSA) also stimulated FN matrix assembly and this effect was reduced by function-blocking antibodies against the receptor for AGE (RAGE). These results indicate that cells respond to AGEs by increasing matrix assembly and that RAGE is involved in this response. This raises the possibility that the accumulation of ECM during the progression of fibrosis may be enhanced by cell interactions with AGEs on a glycated ECM. Keywords Animals, Mice, Extracellular Matrix, Humans, Models, Biological, Signal Transduction, Amino Acid Sequence, Oligopeptides, Gene Expression, Rats, NIH 3T3 Cells, Fibronectins, Integrins, Mesangial Cells, Antibodies, Neutralizing, Cattle, Cell Line, Transformed, Fibrosis, Glycation End Products, Advanced, Pyruvaldehyde, Receptor for Advanced Glycation End Products, Serum Albumin, Bovine Journal Matrix Biol Volume 59 Pages 39-53 Date Published 2017 May ISSN Number 1569-1802 DOI 10.1016/j.matbio.2016.07.003 Alternate Journal Matrix Biol PMCID PMC5237628 PMID 27425255 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML