PMID- 16374426
OWN - NLM
STAT- MEDLINE
DCOM- 20060302
LR  - 20220321
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 69
IP  - 1
DP  - 2006 Jan
TI  - Monocyte chemoattractant protein-1 promotes the development of diabetic renal 
      injury in streptozotocin-treated mice.
PG  - 73-80
AB  - Diabetic nephropathy involves a renal inflammatory response induced by the 
      diabetic milieu. Macrophages accumulate in diabetic kidneys in association with 
      the local upregulation of monocyte chemoattractant protein-1 (MCP-1); however, 
      the contribution of macrophages to renal injury and the importance of MCP-1 to 
      their accrual are unclear. Therefore, we examined the progression of 
      streptozotocin (STZ)-induced diabetic nephropathy in mice deficient in MCP-1 in 
      order to explore the role of MCP-1-mediated macrophage accumulation in the 
      development of diabetic kidney damage. Renal pathology was examined at 2, 8, 12 
      and 18 weeks after STZ treatment in MCP-1 intact (+/+) and deficient (-/-) mice 
      with equivalent blood glucose and hemoglobin A1c levels. In MCP-1(+/+) mice, the 
      development of diabetic nephropathy was associated with increased kidney MCP-1 
      production, which occurred mostly in tubules, consistent with our in vitro 
      finding that elements of the diabetic milieu (high glucose and advanced glycation 
      end products) directly stimulate tubular MCP-1 secretion. Diabetes of 18 weeks 
      resulted in albuminuria and elevated plasma creatinine in MCP-1(+/+) mice, but 
      these aspects of renal injury were largely suppressed in MCP-1(-/-) mice. 
      Protection from nephropathy in diabetic MCP-1(-/-) mice was associated with 
      marked reductions in glomerular and interstitial macrophage accumulation, 
      histological damage and renal fibrosis. Diabetic MCP-1(-/-) mice also had a 
      smaller proportion of kidney macrophages expressing markers of activation 
      (inducible nitric oxide synthase or sialoadhesin) compared to diabetic MCP-1(+/+) 
      mice. In conclusion, our study demonstrates that MCP-1-mediated macrophage 
      accumulation and activation plays a critical role in the development of 
      STZ-induced mouse diabetic nephropathy.
FAU - Chow, F Y
AU  - Chow FY
AD  - Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Nikolic-Paterson, D J
AU  - Nikolic-Paterson DJ
FAU - Ozols, E
AU  - Ozols E
FAU - Atkins, R C
AU  - Atkins RC
FAU - Rollin, B J
AU  - Rollin BJ
FAU - Tesch, G 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  - 5W494URQ81 (Streptozocin)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*physiology
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Diabetic Nephropathies/*etiology
MH  - Kidney/pathology
MH  - Macrophage Activation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Streptozocin
EDAT- 2005/12/24 09:00
MHDA- 2006/03/03 09:00
CRDT- 2005/12/24 09:00
PHST- 2005/12/24 09:00 [pubmed]
PHST- 2006/03/03 09:00 [medline]
PHST- 2005/12/24 09:00 [entrez]
AID - S0085-2538(15)51312-4 [pii]
AID - 10.1038/sj.ki.5000014 [doi]
PST - ppublish
SO  - Kidney Int. 2006 Jan;69(1):73-80. doi: 10.1038/sj.ki.5000014.