PMID- 12761250
OWN - NLM
STAT- MEDLINE
DCOM- 20030820
LR  - 20190607
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 14
IP  - 6
DP  - 2003 Jun
TI  - Anti-monocyte chemoattractant protein-1 gene therapy attenuates renal injury 
      induced by protein-overload proteinuria.
PG  - 1496-505
AB  - It has been postulated that protein filtered through glomeruli activates tubular 
      epithelial cells, which secrete vasoactive and inflammatory substances including 
      chemokines, leading to tubulointerstitial renal injury. The present study was 
      designed to investigate the role of monocyte chemoattractant protein-1 (MCP-1) in 
      this process and to evaluate the effectiveness of a kidney-targeted gene transfer 
      technique using hydrodynamic pressure. Naked plasmid encoding 7ND (an MCP-1 
      antagonist) or a control plasmid was introduced into the left kidney of rats. 
      Three days after gene transfer (day 0), intraperitoneal administration of bovine 
      serum albumin (10 mg/g body wt per day) was started and continued for 14 or 21 d. 
      RT-PCR showed that 7ND mRNA was expressed only in the gene-transfected kidney. 
      Immunostaining showed that 7ND protein was localized in the interstitial cells. 
      Macrophage infiltration was significantly reduced in the left kidney of rats 
      treated with 7ND on days 14 and 21. In the right kidney, such effects were not 
      observed. 7ND also attenuated tubular damage and decreased the number of 
      apoptotic cells. Computer-assisted analysis revealed that the areas positively 
      stained for alpha-smooth muscle actin (alpha SMA), fibronectin-EDA, type I 
      collagen, and collagen fibrils were significantly reduced in the 7ND-treated 
      kidney on day 21. Furthermore, 7ND gene therapy significantly reduced MCP-1 and 
      TGF-beta 1 mRNA expression. These results demonstrate that MCP-1 plays an 
      important role in the development of tubulointerstitial inflammation, tubular 
      damage, and fibrosis induced by proteinuria. The fact that 7ND gene therapy had 
      little effect on the contralateral kidney indicates that 7ND acted locally. This 
      strategy may have a potential usefulness as a gene therapy against 
      tubulointerstitial renal injury.
FAU - Shimizu, Hideaki
AU  - Shimizu H
AD  - Division of Clinical Immunology, Department of Medicine, Nagoya University 
      Graduate School of Medicine, Nagoya, Japan.
FAU - Maruyama, Shoichi
AU  - Maruyama S
FAU - Yuzawa, Yukio
AU  - Yuzawa Y
FAU - Kato, Tomomi
AU  - Kato T
FAU - Miki, Yusuke
AU  - Miki Y
FAU - Suzuki, Satoshi
AU  - Suzuki S
FAU - Sato, Waichi
AU  - Sato W
FAU - Morita, Yoshiki
AU  - Morita Y
FAU - Maruyama, Hiroki
AU  - Maruyama H
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Matsuo, Seiichi
AU  - Matsuo S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proteins)
RN  - 27432CM55Q (Serum Albumin, Bovine)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*antagonists & inhibitors/*genetics
MH  - *Gene Deletion
MH  - *Genetic Therapy
MH  - Kidney/*pathology
MH  - Male
MH  - Proteins/metabolism
MH  - Proteinuria/chemically induced/*pathology/*therapy
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Serum Albumin, Bovine
EDAT- 2003/05/23 05:00
MHDA- 2003/08/21 05:00
CRDT- 2003/05/23 05:00
PHST- 2003/05/23 05:00 [pubmed]
PHST- 2003/08/21 05:00 [medline]
PHST- 2003/05/23 05:00 [entrez]
AID - 10.1097/01.asn.0000069223.98703.8e [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2003 Jun;14(6):1496-505. doi: 
      10.1097/01.asn.0000069223.98703.8e.