Dysfunction of dermal fibroblasts induced by advanced glycation end-products (AGEs) and the contribution of a nonspecific interaction with cell membrane and AGEs

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

“…153 Accumulation of AGEs on collagen in the ECM of skin has been widely studied. 152,154,155 Glycosylation of collagen leads to increased crosslinking between collagen fibers, increased stiffness, decreased solubility, and decreased susceptibility to proteolysis. 152,155,156 Some authors highlight differences between the collagen cross-linking due to DM compared with aging, stressing that diabetic crosslinking is more extensive and causes a further decrease in solubility.…”

“…AGEs have also been found to accumulate on elastin fibers within skin that has undergone solar elastosis. 154 AGEs generate active oxygen-free radical species during UVA irradiation, thereby increasing damage to and photoaging of the skin. 154 With regard to wound healing, nonenzymatic glycosylation of collagen leads to impaired fibroblastinduced contraction.…”

“…154 AGEs generate active oxygen-free radical species during UVA irradiation, thereby increasing damage to and photoaging of the skin. 154 With regard to wound healing, nonenzymatic glycosylation of collagen leads to impaired fibroblastinduced contraction. 152 During ECM remodeling in the normal healing process, contraction of collagen matrices is associated with downregulation of type I collagen and upregulation of MMPs by fibroblasts.…”

Combining nano-physical and computational investigations to understand the nature of “aging” in dermal collagen

“…Its more reactive open chain form only composes 0.002% of glucose molecules in vivo; therefore, significant collagen cross-linking requires a prolonged exposure to glucose. 23 A number of other AGE cross-links can also form, such as pentosidine, 24 DOGDIC (deoxyglucosone lysine-arginine cross-link), MOLD (methylglyoxal lysine dimer) and GOLD (glyoxal lysine dimer), 17,21 among others ( Figure 2). Deoxyglucosone and glyoxal are formed due to fragmentation of the Amadori product (an intermediate precursor product to an AGE in the Maillard reaction) and are highly reactive, although they are found in very small concentrations in vivo.…”

“…Glucosepane is present in human tissues at levels 10-1,000 times higher than any other cross-linking AGE, and is currently considered to be the most important cross-linking AGE. 23 Glucosepane has two hydroxyl groups, leading to the possibility of water interaction due to its hydrophilic nature, as illustrated by Figure 7B. Therefore, as the volunteer ages and more glucosepane cross-links accumulate, more water molecules may be bound within the fibril as shown in Figure 7B.…”