Methylglyoxal-modified collagen promotes myofibroblast differentiation

• Published in: Matrix biology 2010-07, Vol.29 (6), p.537-548
• Main Authors: Yuen, Amy, Laschinger, Carol, Talior, Ilana, Lee, Wilson, Chan, Matthew, Birek, Juliana, Young, Edmond W.K., Sivagurunathan, Konesh, Won, Emily, Simmons, Craig A., McCulloch, C.A.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Biomarkers - metabolism; Cadherins; Cadherins - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell migration; Cell Movement - drug effects; Cells, Cultured; Collagen - metabolism; Collagen - pharmacology; Dose-Response Relationship, Drug; Extracellular Matrix - metabolism; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - physiology; Fibronectins - metabolism; Fibrosis - pathology; Gels - metabolism; Humans; Integrins; Muscle, Smooth - metabolism; Myocardium - cytology; Myofibroblasts - metabolism; Pyruvaldehyde - metabolism; Pyruvaldehyde - pharmacology; Transforming Growth Factor beta - metabolism
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2010.04.004

Fibrosis is a frequent complication of diabetes mellitus in many organs and tissues but the mechanism of how diabetes-induced glycation of extracellular matrix proteins impacts the formation of fibrotic lesions is not defined. As fibrosis is mediated by myofibroblasts, we investigated the effect of collagen glycation on the conversion of human cardiac fibroblasts to myofibroblasts. Collagen glycation was modeled by the glucose metabolite, methylglyoxal (MGO). Cells cultured on MGO-treated collagen exhibited increased activity of the α-smooth muscle actin promoter and enhanced expression of α-smooth muscle actin, ED-A fibronectin and cadherin, which are markers for myofibroblasts. In cells remodeling floating or stress-relaxed collagen gels, MGO treatment promoted more contraction (p