PMID- 14738871
OWN - NLM
STAT- MEDLINE
DCOM- 20040224
LR  - 20211122
IS  - 0014-4800 (Print)
IS  - 0014-4800 (Linking)
VI  - 76
IP  - 1
DP  - 2004 Feb
TI  - Fluvastatin prevents nephropathy likely through suppression of connective tissue 
      growth factor-mediated extracellular matrix accumulation.
PG  - 66-75
AB  - Diabetic nephropathy is related to glomerular extracellular matrix (ECM) 
      accumulation that leads to glomerulosclerosis. Fluvastatin as a lipid-lowering 
      medicine significantly prevents diabetic nephropathy, probably not only through 
      its lipid-lowering action, but also mainly through its direct suppression of 
      glomerular ECM accumulation. To test this hypothesis, in the present study, a 
      five-sixths nephrectomized (5/6Nx) rat model to induce a renal ECM accumulation 
      without coexistence of hyperlipidemia was used to investigate the effect of 
      fluvastatin on renal function, glomerular ECM accumulation and expression of 
      connective tissue growth factor (CTGF). 5/6Nx induced a significant nephropathy 
      in rats at 13 weeks, indicated by renal dysfunction including increases in blood 
      urine nitrogen, creatinine and urinary protein excretion, and renal 
      histopathological changes. Administration of fluvastatin significantly prevented 
      the renal dysfunction and histological abnormalities in the 5/6Nx rats. 
      Furthermore, both significant suppression of matrix metalloproteinases (MMPs) 
      activity such as MMP-2 and significant activation of tissue inhibitors of MMP 
      (TIMPs) such as TIMP-2 observed in the 5/6Nx rats were almost completely 
      prevented by fluvastatin, resulting in a significant prevention of glomerular ECM 
      accumulation. For upstream mediator of ECM accumulation, 5/6Nx significantly 
      up-regulated CTGF mRNA expression, but fluvastatin treatment prevented CTGF 
      up-regulation. These results suggest that fluvastatin, as one of well-known 
      lipid-lowering agents, plays an important role in the prevention of nephropathy, 
      likely through suppression of CTGF-mediated ECM accumulation. Therefore, 
      fluvastatin may be a potential candidate for developing a pharmaceutical approach 
      to the prevention of diabetic nephropathy due to its both lipid-lowering and 
      direct anti-renal ECM accumulation actions.
FAU - Song, Ye
AU  - Song Y
AD  - Department of Pathology, Institute of Frontier Medical Science, Jilin University, 
      Changchun, PR China.
FAU - Li, Cai
AU  - Li C
FAU - Cai, Lu
AU  - Cai L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (CCN2 protein, rat)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Indoles)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - 4L066368AS (Fluvastatin)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Animals
MH  - Anticholesteremic Agents/*therapeutic use
MH  - Blood Urea Nitrogen
MH  - Connective Tissue Growth Factor
MH  - Creatinine/urine
MH  - Disease Models, Animal
MH  - Extracellular Matrix/*metabolism
MH  - Fatty Acids, Monounsaturated/*therapeutic use
MH  - Fluvastatin
MH  - Immediate-Early Proteins/*biosynthesis/genetics
MH  - Indoles/*therapeutic use
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis/genetics
MH  - Kidney Failure, Chronic/metabolism/pathology/*prevention & control
MH  - Kidney Glomerulus/drug effects/metabolism/pathology
MH  - Male
MH  - Matrix Metalloproteinase Inhibitors
MH  - Nephrectomy
MH  - Proteinuria
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis
MH  - Up-Regulation
EDAT- 2004/01/24 05:00
MHDA- 2004/02/26 05:00
CRDT- 2004/01/24 05:00
PHST- 2004/01/24 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2004/01/24 05:00 [entrez]
AID - S0014480003001059 [pii]
AID - 10.1016/j.yexmp.2003.08.002 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 2004 Feb;76(1):66-75. doi: 10.1016/j.yexmp.2003.08.002.