Title |
Presence of Diabetic Complications in Type 1 Diabetic Patients Correlates with Low Expression of Mononuclear Cell AGE-Receptor-1 and Elevated Serum AGE
|
---|---|
Published in |
Molecular Medicine, March 2001
|
DOI | 10.1007/bf03401949 |
Pubmed ID | |
Authors |
Ci-jiang He, Theodore Koschinsky, Christina Buenting, Helen Vlassara |
Abstract |
Receptors for advanced glycation endproducts (AGE-R) mediate AGE turnover, but can also trigger inflammatory genes that promote diabetic tissue injury and diabetic complications (DC). High AGE levels and reduced AGE-R sites in kidneys of NOD mice prone to type 1 diabetes (T1D) and to renal disease (RD) suggested that impaired AGE-R function may contribute to RD in these mice. In this study, after confirming reduced AGE-R1 expression in NOD mouse peritoneal macrophages, we tested for differences in AGE-R1, -R2, and -R3 gene expression in 54 human subjects by RT-PCR and Western analysis. Fresh peripheral blood mononuclear cells (PBMN) were isolated from 36 persons: 18 T1D patients with severe RD (DC); 11 age-and DM-duration matched patients without DC (n-DC); and 7 normal volunteers (NL). EBV-transformed lymphoblasts were obtained from an additional 18 subjects (12 T1D patients, 6 with and 6 without DC, and 6 nondiabetics). AGE-R1 mRNA and protein of PBMN from n-DC patients were enhanced (p < .05 versus NL) in proportion to serum AGE levels (sAGE) (p < .005 versus NL). In contrast, PBMN from DC patients exhibited no up-regulation of AGE-R1 mRNA or protein, despite higher sAGE levels (p < .005 versus NL). A similar unresponsiveness in AGE-R1 gene expression was observed in EBV-transformed lymphoblasts from DC patients versus NL (p < .01), but not in n-DC (p = NS). AGE-R2 and -R3 mRNA and protein levels were enhanced in both T1D groups (DC > n-DC) (n-DC AGE-R3, p < .05, DC AGE-R3, p < .05) compared to NL. AGE-R2 mRNA levels correlated with sAGE levels (r = .61, p < .05), and with creatinine clearance (r = -.63, p < .05). No differences were noted in AGE-R2 and -R3 mRNA expression in cultured cells. The consistent pattern of elevated serum AGE and low expression of AGE-R1 gene in macrophages from T1D mice (NOD), fresh PBMN and EBV-transformed cells from T1D patients with advanced DC suggests ineffective regulation of R1-mediated AGE turnover, possibly of genetic basis. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 21 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 5 | 24% |
Researcher | 4 | 19% |
Student > Bachelor | 3 | 14% |
Student > Postgraduate | 2 | 10% |
Student > Ph. D. Student | 1 | 5% |
Other | 2 | 10% |
Unknown | 4 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 5 | 24% |
Agricultural and Biological Sciences | 5 | 24% |
Biochemistry, Genetics and Molecular Biology | 3 | 14% |
Sports and Recreations | 1 | 5% |
Engineering | 1 | 5% |
Other | 0 | 0% |
Unknown | 6 | 29% |