The Receptor for Advanced Glycation End Products Is Highly Expressed in the Skin and Upregulated by Advanced Glycation End Products and Tumor Necrosis Factor-Alpha

Abstract

Advanced glycation end products (AGEs) form non-enzymatically from reactions of proteins with reducing sugars. In the skin, AGEs were reported to accumulate in dermal elastin and collagens and to interact nonspecifically with the cell membrane of dermal fibroblasts. Therefore, AGEs may influence the process of skin aging. We investigated the presence of the AGE receptor RAGE in skin and the influence of AGEs on receptor expression and the formation of extracellular matrix (ECM). Sections of sun-protected and sun-exposed skin were analyzed with monoclonal antibodies against (RAGE), heat-shock protein 47, factor XIIIa, CD31, and CD45. RAGE was mainly expressed in fibroblasts, dendrocytes, and keratinocytes and to a minor extent in endothelial and mononuclear cells. Human foreskin fibroblasts (HFFs) highly expressed RAGE on the protein and mRNA level when analyzed by quantitative Western blotting and real-time PCR. Incubation of HFFs with the specific RAGE ligand Nepsilon-(carboxymethyl)lysine-modified BSA (CML-BSA) and tumor necrosis factor-alpha resulted in significant upregulation of RAGE expression. CML-BSA induced a mildly profibrogenic pattern, increasing connective tissue growth factor, transforming growth factor-beta (TGF-beta) 1, and procollagen-alpha1(I) mRNA, whereas expression of matrix metalloproteinase (MMP)-1, -2, -3, and -12 was unaffected. We conclude that in HFFs, AGE-RAGE interactions may influence the process of skin aging through mild stimulation of ECM gene expression.

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

“…Due to the critical role of RAGE in regulating diabetes-associated chronic inflammations, most research on RAGE has been focused on diabetes-related organs and cells. Although several studies have reported RAGE expression in some epithelial cells, including eye epithelial cells (55,56), lung epithelial cells (38), and skin cells (57), so far there is no direct evidence of RAGE in the intestinal epithelium, in particular under inflammatory conditions. In this study, we demonstrated that RAGE is expressed in both cultured human intestinal epithelial cells and normal and inflammatory intestinal tissues.…”

Inhibition of Advanced Glycation End Products Formation by Mangifera indica Leaf Extract

“…In addition, AGEs induce fibroblast apoptosis by adducting to AGE receptors on the cell (Pageon, Bakala, Monnier, & Asselineau, 2007). These phenomena are also thought to be related to skin aging (Lohwasser, Neureiter, Weigle, Kirchner, & Schuppan, 2006). Therefore, in recent years, the role of AGEs has been increasingly discussed in the skin aging, and the inhibition of AGEs formation can be one of the effective strategies for direct alleviation of the development of novel antiaging cosmeceutical ingredients.…”

Role of the receptor for advanced glycation end products inhepatic fbrosis

“…Control BSA was incubated in parallel in the absence of D-glucose. Preparation of CML-modified BSA was carried out as previously described [20] . Glycation of AGE-BSA and CML-BSA was determined using the 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay [21] , resulting in a 45.6% and 36.5% glycation of lysines for AGE-BSA and CML-BSA, respectively.…”