TY - JOUR
T1 - The involvement of advanced glycation endproducts (AGEs) in renal injury of diabetic glomerulosclerosis
T2 - Association with phenotypic change in renal cells and infiltration of immune cells
AU - Mao, Yonghui
AU - Ootaka, Tetsuya
AU - Saito, Takao
AU - Sato, Hiroshi
AU - Sato, Toshinobu
AU - Ito, Sadayoshi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/9
Y1 - 2003/9
N2 - Background. Glycation of proteins is regarded as one of the major causes of the progression of diabetic nephropathy (DN) and of the phenotypic changes in glomerular mesangial cells (MC) and the cellular infiltration that occurs in MC from DN. It thus is very important to study the interrelationships and interaction between these causes. Methods. The localization of advanced glycation endproducts (AGEs), cytoskeletal proteins, and immune cell infiltration was evaluated by immunohistochemical study in patients with DN. Results. Nε-(carboxymethyl)lysine (CML), α-smooth muscle actin (SMA), and low-molecular-weight caldesmon (L-CLD) were localized in the mesangial area in DN. The intensity of mesangial SMA and L-CLD expression was significantly correlated with the index of diabetic glomerulosclerosis (IDGS), while the expression of pentosidine was correlated with the IDGS and with 24-h urinary protein. Pentosidine was localized in glomerular basement membrane (GBM) only in DN and had a significant correlation with the mesangial expression of SMA and L-CLD. Pyrraline deposition on the tubular basement membrane, and the expression of SMA and L-CLD, and the infiltration of immune cells were observed in interstitial areas in DN. The intensity of L-CLD expression had a close relationship with pyrraline deposition and immune cell infiltration. The expression of SMA and L-CLD in interstitial areas was significantly correlated with the percent interstitial volume. Conclusions. AGEs are involved in renal injury in DN, and their effect is, at least in part, exercised via phenotypic changes in intrinsic renal cells and by the infiltration of immune cells.
AB - Background. Glycation of proteins is regarded as one of the major causes of the progression of diabetic nephropathy (DN) and of the phenotypic changes in glomerular mesangial cells (MC) and the cellular infiltration that occurs in MC from DN. It thus is very important to study the interrelationships and interaction between these causes. Methods. The localization of advanced glycation endproducts (AGEs), cytoskeletal proteins, and immune cell infiltration was evaluated by immunohistochemical study in patients with DN. Results. Nε-(carboxymethyl)lysine (CML), α-smooth muscle actin (SMA), and low-molecular-weight caldesmon (L-CLD) were localized in the mesangial area in DN. The intensity of mesangial SMA and L-CLD expression was significantly correlated with the index of diabetic glomerulosclerosis (IDGS), while the expression of pentosidine was correlated with the IDGS and with 24-h urinary protein. Pentosidine was localized in glomerular basement membrane (GBM) only in DN and had a significant correlation with the mesangial expression of SMA and L-CLD. Pyrraline deposition on the tubular basement membrane, and the expression of SMA and L-CLD, and the infiltration of immune cells were observed in interstitial areas in DN. The intensity of L-CLD expression had a close relationship with pyrraline deposition and immune cell infiltration. The expression of SMA and L-CLD in interstitial areas was significantly correlated with the percent interstitial volume. Conclusions. AGEs are involved in renal injury in DN, and their effect is, at least in part, exercised via phenotypic changes in intrinsic renal cells and by the infiltration of immune cells.
KW - Advanced glycation endproducts
KW - Diabetic nephropathy
KW - L-caldesmon
KW - Leukocytes
KW - α-Smooth muscle actin
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U2 - 10.1007/s10157-003-0245-z
DO - 10.1007/s10157-003-0245-z
M3 - Article
C2 - 14586716
AN - SCOPUS:0141960945
VL - 7
SP - 201
EP - 209
JO - Clinical and Experimental Nephrology
JF - Clinical and Experimental Nephrology
SN - 1342-1751
IS - 3
ER -