PMID- 16263740
OWN - NLM
STAT- MEDLINE
DCOM- 20060713
LR  - 20171116
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 21
IP  - 2
DP  - 2006 Feb
TI  - Role of receptor for advanced glycation end-products and signalling events in 
      advanced glycation end-product-induced monocyte chemoattractant protein-1 
      expression in differentiated mouse podocytes.
PG  - 299-313
AB  - BACKGROUND: Upregulation of local monocyte chemoattractant protein-1 (MCP-1) 
      production is involved in glomerular damage through macrophage recruitment and 
      activation in diabetic nephropathy. Treatment of db/db mice with soluble receptor 
      for advanced glycation end-products (RAGE) prevented recruitment of macrophages 
      to the glomeruli and reduced albuminuria, suggesting that binding of ligands and 
      RAGE may be involved in MCP-1 expression. Therefore, we investigated the role of 
      advanced glycation end-products (AGEs) in MCP-1 production by podocytes and 
      signalling events after RAGE activation. METHODS: MCP-1 gene and protein 
      expression were examined by using reverse transcription-polymerase chain reaction 
      and enzyme-linked immunosorbent assay in differentiated mouse podocytes. 
      Dichlorofluorescein-sensitive intracellular reactive oxygen species (ROS) 
      generation was measured by confocal microscopy. RAGE, phosphorylation of 
      mitogen-activated protein kinases, nuclear factor (NF)-kappaB, c-Jun and Sp1 were 
      studied using western blotting and immunocytochemistry. RESULTS: Both 
      differentiated and undifferentiated podocytes expressed RAGE. MCP-1 was induced 
      by AGEs and carboxymethyllysine (CML) in a time-dependent and dose-dependent 
      manner in differentiated podocytes. Neutralizing antibody for RAGE suppressed 
      AGE- and CML-induced MCP-1 production. AGEs and CML rapidly generated 
      intracellular ROS in podocytes. Blocking of ROS by using N-acetyl-l-cysteine 
      abolished CML and H(2)O(2)-induced MCP-1 expression. Phosphorylated extracellular 
      signal-regulated kinase (ERK) was found in podocytes incubated with CML and was 
      prevented by N-acetyl-l-cysteine or 7'-amino 4 [trifluoromethyl]. PD98059, an 
      inhibitor of ERK, partially prevented CML-induced MCP-1 gene expression. 
      NF-kappaB and Sp1 were translocated into the nucleus after podocytes were 
      incubated with CML for 60 min. Parthenolide and mithramycin A, inhibitors of 
      NF-kappaB and Sp1, respectively, abolished CML-induced MCP-1 gene expression in a 
      dose-dependent manner. CONCLUSIONS: These results suggest that AGEs and CML 
      induce MCP-1 expression in podocytes through activation of RAGE and generation of 
      intracellular ROS. NF-kappaB and Sp1 regulate MCP-1 gene transcription.
FAU - Gu, Leyi
AU  - Gu L
AD  - Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, 
      Japan.
FAU - Hagiwara, Shinji
AU  - Hagiwara S
FAU - Fan, Qiuling
AU  - Fan Q
FAU - Tanimoto, Mitsuo
AU  - Tanimoto M
FAU - Kobata, Mami
AU  - Kobata M
FAU - Yamashita, Michifumi
AU  - Yamashita M
FAU - Nishitani, Tomohito
AU  - Nishitani T
FAU - Gohda, Tomohito
AU  - Gohda T
FAU - Ni, Zhaohui
AU  - Ni Z
FAU - Qian, Jiaqi
AU  - Qian J
FAU - Horikoshi, Satoshi
AU  - Horikoshi S
FAU - Tomino, Yasuhiko
AU  - Tomino Y
LA  - eng
PT  - Journal Article
DEP - 20051101
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Chemokine CCL2)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Membrane Proteins/*physiology
MH  - Mice
MH  - Podocytes/cytology/*metabolism
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*physiology
EDAT- 2005/11/03 09:00
MHDA- 2006/07/14 09:00
CRDT- 2005/11/03 09:00
PHST- 2005/11/03 09:00 [pubmed]
PHST- 2006/07/14 09:00 [medline]
PHST- 2005/11/03 09:00 [entrez]
AID - gfi210 [pii]
AID - 10.1093/ndt/gfi210 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2006 Feb;21(2):299-313. doi: 10.1093/ndt/gfi210. Epub 
      2005 Nov 1.