N epsilon(Carboxymethyl)Lysine-Induced Mesangial Cell Activation / 대한신장학회잡지
Korean Journal of Nephrology
;
: 20-28, 2002.
Article
in Korean
| WPRIM
| ID: wpr-126481
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Rage
/
Enzyme-Linked Immunosorbent Assay
/
Plasminogen Activators
/
Up-Regulation
/
Blotting, Western
/
Risk Factors
/
Transforming Growth Factor beta
/
Fibronectins
/
Plasminogen Activator Inhibitor 1
/
Galectin 3
Type of study:
Etiology study
/
Risk factors
Limits:
Animals
Language:
Korean
Journal:
Korean Journal of Nephrology
Year:
2002
Type:
Article
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