PMID- 14675042
OWN - NLM
STAT- MEDLINE
DCOM- 20040928
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 65
IP  - 1
DP  - 2004 Jan
TI  - Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state 
      and progressive renal injury.
PG  - 116-28
AB  - BACKGROUND: Macrophage-mediated renal injury has been implicated in progressive 
      forms of glomerulonephritis; however, a role for macrophages in type 2 diabetic 
      nephropathy, the major cause of end-stage renal failure, has not been 
      established. Therefore, we examined whether macrophages may promote the 
      progression of type 2 diabetic nephropathy in db/db mice. METHODS: The incidence 
      of renal injury was examined in db/db mice with varying blood sugar and lipid 
      levels at 8 months of age. The association of renal injury with the accumulation 
      of kidney macrophages was analyzed in normal db/+ and diabetic db/db mice at 2, 
      4, 6, and 8 months of age. RESULTS: In db/db mice, albuminuria and increased 
      plasma creatinine correlated with elevated blood glucose and hemoglobin A1c 
      (HbA1c) levels but not with obesity or hyperlipidemia. Progressive diabetic 
      nephropathy in db/db mice was associated with increased kidney macrophages. 
      Macrophage accumulation and macrophage activation in db/db mice correlated with 
      hyperglycemia, HbA1c levels, albuminuria, elevated plasma creatinine, glomerular 
      and tubular damage, renal fibrosis, and kidney expression of macrophage 
      chemokines [monocyte chemoattractant protein-1 (MCP-1), osteopontin, migration 
      inhibitory factor (MIF), monocyte-colony-stimulating factor (M-CSF)]. The accrual 
      and activation of glomerular macrophages also correlated with increased 
      glomerular IgG and C3 deposition, which was itself dependent on hyperglycemia. 
      CONCLUSION: Kidney macrophage accumulation is associated with the progression of 
      type 2 diabetic nephropathy in db/db mice. Macrophage accumulation and activation 
      in diabetic db/db kidneys is associated with prolonged hyperglycemia, glomerular 
      immune complex deposition, and increased kidney chemokine production, and raises 
      the possibility of specific therapies for targeting macrophage-mediated injury in 
      diabetic nephropathy.
FAU - Chow, Fiona
AU  - Chow F
AD  - Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Ozols, Elyce
AU  - Ozols E
FAU - Nikolic-Paterson, David J
AU  - Nikolic-Paterson DJ
FAU - Atkins, Robert C
AU  - Atkins RC
FAU - Tesch, Gregory H
AU  - Tesch GH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spp1 protein, mouse)
RN  - 106441-73-0 (Osteopontin)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - Diabetes Mellitus/epidemiology/immunology/pathology
MH  - Diabetes Mellitus, Type 2/epidemiology/*immunology/*pathology
MH  - Diabetic Nephropathies/epidemiology/*immunology/*pathology
MH  - Female
MH  - Fibrosis
MH  - Gene Expression/immunology
MH  - Hyperglycemia/immunology/pathology
MH  - Incidence
MH  - Macrophage Colony-Stimulating Factor/genetics
MH  - Macrophage Migration-Inhibitory Factors/genetics
MH  - Macrophages/immunology/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Obesity
MH  - Osteopontin
MH  - Sialoglycoproteins/genetics
EDAT- 2003/12/17 05:00
MHDA- 2004/09/29 05:00
CRDT- 2003/12/17 05:00
PHST- 2003/12/17 05:00 [pubmed]
PHST- 2004/09/29 05:00 [medline]
PHST- 2003/12/17 05:00 [entrez]
AID - S0085-2538(15)49682-6 [pii]
AID - 10.1111/j.1523-1755.2004.00367.x [doi]
PST - ppublish
SO  - Kidney Int. 2004 Jan;65(1):116-28. doi: 10.1111/j.1523-1755.2004.00367.x.