N epsilon(Carboxymethyl)Lysine-Induced Mesangial Cell Activation.
- Author:
Hyun Jin LIM
1
;
Jae Sook SONG
;
Hun Joo HA
;
Hi Bahl LEE
Author Information
1. Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Seoul, Korea. hblee@seoul.com
- Publication Type:Original Article
- Keywords:
Advanced glycosylation end products;
N epsilon(carboxymethyl)lysine;
Proliferation;
Fibronectin;
Receptor for AGE;
Galectin-3;
Mesangial cells
- MeSH:
Animals;
Blotting, Western;
Cell Proliferation;
Diabetic Nephropathies;
Enzyme-Linked Immunosorbent Assay;
Fibronectins;
Galectin 3;
Glucose;
Glycosylation End Products, Advanced;
Kidney;
Mesangial Cells*;
Plasminogen Activator Inhibitor 1;
Plasminogen Activators;
Rage;
Rats;
Risk Factors;
Transforming Growth Factor beta;
Up-Regulation;
Advanced Glycosylation End Product-Specific Receptor
- From:Korean Journal of Nephrology
2002;21(1):20-28
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Advanced glycation end products (AGE) are independent risk factors in the development and progression of diabetic nephropathy. Receptor for AGE(RAGE) is considered the main receptor involved in AGE-induced cell activation. Galectin-3, another AGE receptor, has recently been found upregulated in mesangial cells(MC) cultured under high glucose and in diabetic rat kidneys. N epsilon(carboxymethyl)lysine(CML) is a well characterized AGE but its role in MC activation is unknown. The present study examined the effects of CML on MC proliferation and extracellular matrix(ECM) secretion. METHODS: Synchronized rat MC were stimulated with different concentrations of CML-bovine serum albumin(BSA), control BSA, and transforming growth factor-beta(TGF-beta) for up to 72 hours. Cell proliferation was measured by [3H]-thymidine incorporation. Fibronectin, TGF-beta, plasminogen activator inhibitor(PAI)-1 secreted into the media and RAGE and galectin-3 expression in MC were measured by Western blot analysis and ELISA. RESULTS: 1,000 micro /mL of CML-BSA decreased [3H]-thymidine incorporation by MC at 48 hours and 10 ng/mL TGF-beta at 24 and 48 hours. CML-BSA 100 and 1,000 micro /mL, control BSA 1,000 micro /mL, and TGF-beta 10 ng/mL increased fibronectin secretion at 48 hours. CML-BSA up to 1,000 micro /mL did not affect TGF-beta or PAI-1 secretion. TGF-beta 10 ng/mL, however, significantly increased PAI-1 secretion. Cultured MC expressed both RAGE and galectin-3. CML-BSA 100 micro /mL upregulated galectin-3 expression. CONCLUSION: CML-BSA decreased MC proliferation and increased fibronectin secretion, suggesting that CML may lead to ECM accumulation and glomerulosclerosis in diabetic animals. MC express RAGE and galectin-3 constitutively and CML-induced galectin-3 upregulation may have a role in AGE-induced MC activation.
