Two dicarbonyl compounds, 3-deoxyglucosone and methylglyoxal, differentially modulate dermal fibroblasts.
Advanced glycation endproducts accumulate on long-lived proteins such as collagens as a function of diet and age and mediate the cross-linking of those proteins causing changes in collagen pathophysiology resulting in the disruption of normal collagen matrix remodeling. Two commonly studied advanced glycation endproduct precursors 3-deoxyglucosone and methylglyoxal were investigated for their role in the modification of collagen and on extracellular matrix expression. Fibroblasts cultured on methylglyoxal cross-linked matrices increased the expression of collagen, active TGF-beta1, beta1-integrin, and decreased Smad7; whereas 3-deoxyglucosone decreased collagen, active TGF-beta1, beta1-integrin but increased Smad7. Purified collagen modified by 3-deoxyglucosone or methylglyoxal had different molecular weights; methylglyoxal increased the apparent molecular weight by approximately 20 kDa, whereas 3-deoxyglucosone did not. The differences in collagen expression by 3-deoxyglucosone and methylglyoxal raise the provocative idea that a genetic or environmental background leading to the predominance of one of these advanced glycation endproduct precursors may precipitate a fibrotic or chronic wound in susceptible individuals, particularly in the diabetic.
Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
Sihem
S
Sassi-Gaha
Danielle T
DT
Loughlin
Frank
F
Kappler
Michael L
ML
Schwartz
Bangying
B
Su
Annette M
AM
Tobia
Carol M
CM
Artlett
D002460:Cell Line; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D017127:Glycation End Products, Advanced; D019012:Integrin beta1; D020033:Protein Isoforms; D053773:Transforming Growth Factor beta1; D011765:Pyruvaldehyde; D003094:Collagen; D003847:Deoxyglucose; C016350:3-deoxyglucosone