Korean Journal of Nephrology 2002;21(1):20-28.

원저 : Nε - ( Carboxymethyl ) Lysine - 우혈청 알부민이 흰쥐 사구체 혈관간세포의 활성화에 미치는 영향 (Original articles : Nε - ( Carboxymethyl ) Lysine - Induced Mesangial Cell Activation)

임현진(Hyun Jin Lim),송재숙(Jae Sook Song),하헌주(Hun Joo Ha),이희발(Hi Bahl Lee)

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. Nε-(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-β1(TGF-β1) for up to 72 hours. Cell proliferation was measured by [3H]-thymidine incorporation. Fibronectin, TGF-β1, 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 μg/mL of CML-BSA decreased [3H]-thymidine incorporation by MC at 48 hours and 10 ng/mL TGF-β1 at 24 and 48 hours. CML-BSA 100 and 1,000 μg/mL, control BSA 1,000 μg/mL, and TGF-β1 10 ng/mL increased fibronectin secretion at 48 hours. CML-BSA up to 1,000 μg/mL did not affect TGF-β1 or PAI-1 secretion. TGF-β1 10 ng/mL, however, significantly increased PAI-1 secretion. Cultured MC expressed both RAGE and galectin-3. CML-BSA 100 μg/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. (Korean J Nephrol 2002;21(1):20-28)