PMID- 10412769
OWN - NLM
STAT- MEDLINE
DCOM- 19990915
LR  - 20190131
IS  - 0098-6577 (Print)
IS  - 0098-6577 (Linking)
VI  - 71
DP  - 1999 Jul
TI  - Involvement of MCP-1 and M-CSF in glomerular foam cell formation in ExHC rats.
PG  - S174-7
AB  - BACKGROUND: An increase in glomerular macrophages (MO) is considered a potential 
      effector mechanism by which hypercholesterolemia exacerbates glomerular injury. 
      To investigate the mechanism underlying recruitment of MO into glomeruli, the 
      expression of glomerular monocyte chemoattractant protein-1 (MCP-1) and 
      macrophage colony-stimulating factor (M-CSF) mRNA were examined using a 
      lipid-induced glomerular injury rat model. METHODS: Eight-week-old male ExHC 
      rats, a strain susceptible to hyperlipidemia, were divided into the following 4 
      groups: a control group (C), a high cholesterol diet group (HH), a high 
      cholesterol diet/standard diet group (HN), which were fed a high cholesterol diet 
      for the first 4 weeks and a standard diet for the following 4 weeks, and a 
      probucol-treatment group (PT). Both MCP-1 and M-CSF mRNA expression in glomeruli 
      were analyzed using the RT-PCR method. An additional experimental group (M) fed a 
      high cholesterol diet was administered M-CSF daily for 4 weeks. RESULTS: The 
      expression of MCP-1 mRNA in glomeruli increased accompanied by an increased total 
      serum cholesterol level in HH and HN. However, M-CSF mRNA expression was 
      significantly suppressed at 1 or 2 weeks and gradually increased to almost basal 
      levels. In the PT group, MCP-1 mRNA expression was suppressed. The early 
      suppression of M-CSF mRNA expression was inhibited in PT. Renal histology showed 
      a significant increase in foam cells in glomeruli in HH and HN rats at 4 weeks. 
      HH rats showed increased and expanded foam cells at 8 weeks. In HN rats, however, 
      foam cells decreased significantly after the transfer to a standard diet from a 
      high cholesterol diet. The MCP-1 mRNA expression was suppressed after the 
      transfer. In the PT group, foam cell formation was also suppressed. Foam cells 
      were identified as MO. M-CSF-treatment significantly suppressed foam cell 
      formation in glomeruli when compared with the untreated group levels. CONCLUSION: 
      These findings suggest that hypercholesterolemia stimulated the expression of 
      MCP-1 in glomeruli and attracted the MO into glomeruli. They also suggest that 
      the reduction of hypercholesterolemia after the change in diet or treatment with 
      probucol suppressed glomerular injury by suppressing the glomerular MCP-1 
      expression. M-CSF may suppress the recruitment of MO into glomeruli and foam cell 
      formation at an early stage of hypercholesterolemia-induced glomerular injury.
FAU - Kodama, N
AU  - Kodama N
AD  - Third Department of Internal Medicine, Wakayama Medical College, Japan.
FAU - Otani, H
AU  - Otani H
FAU - Yamada, Y
AU  - Yamada Y
FAU - Mune, M
AU  - Mune M
FAU - Yukawa, S
AU  - Yukawa S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int Suppl
JT  - Kidney international. Supplement
JID - 7508622
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (RNA, Messenger)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - P3CTH044XJ (Probucol)
SB  - IM
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology
MH  - Chemokine CCL2/*genetics
MH  - Cholesterol, Dietary/adverse effects
MH  - Foam Cells/drug effects/*pathology
MH  - Hypercholesterolemia/drug therapy/etiology/*physiopathology
MH  - Kidney Glomerulus/drug effects/metabolism/*pathology
MH  - Macrophage Colony-Stimulating Factor/*genetics/pharmacology
MH  - Male
MH  - Probucol/pharmacology
MH  - Proteinuria/prevention & control/urine
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Rats
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - S0085-2538(15)46633-5 [pii]
PST - ppublish
SO  - Kidney Int Suppl. 1999 Jul;71:S174-7.