High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: possible role of TGF-beta.
BACKGROUND
It has been shown that tubulointerstitial injury correlates well with a decline of renal function. In this study, we investigated the effect of high water intake (HWI) on functional and structural parameters in rats with subtotal nephrectomy.


METHODS
Two weeks after the ablative procedure, rats were divided into two groups. One group received the treatment with HWI (3% sucrose added to drinking water) for eight weeks. Functional parameters were compared with sham-operated control (CONT) or nephrectomized rats without treatment (NX). Remnant kidneys were then assessed histologically for evidence of interstitial fibrosis and glomerulosclerosis.


RESULTS
Creatinine clearance was significantly improved in HWI rats compared with NX rats. Simultaneously, urinary protein was also significantly reduced in HWI rats. HWI predominantly ameliorated interstitial lesions and, to a lesser extent, glomerular lesions. Northern blot analysis demonstrated that transforming growth factor-beta (TGF-beta) mRNA expression was significantly suppressed in HWI rats. In situ hybridization revealed that HWI suppressed TGF-beta mRNA expression mainly in the outer medulla. Fibronectin mRNA was also reduced by the HWI treatment. The changes in TGF-beta and fibronectin mRNA were in parallel with Na+/myo-inositol cotransporter (SMIT) mRNA, which is regulated by extracellular osmolarity. Immunohistochemistry demonstrated that protein expression of TGF-beta and fibronectin coincided with the mRNA expression.


CONCLUSIONS
These results suggest that HWI reduces TGF-beta mRNA expression in medullary interstitium and ameliorates tubulointerstitial injury in rats with reduced renal mass.
Sugiura
T
T
First Department of Medicine, Osaka University School of Medicine, Japan.
Yamauchi
A
A
Kitamura
H
H
Matsuoka
Y
Y
Horio
M
M
Imai
E
E
Hori
M
M
D000818:Animals; D001794:Blood Pressure; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D018076:DNA, Complementary; D004326:Drinking / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000601:surgery / Q000628:therapy; D006360:Heat-Shock Proteins / Q000235:genetics; D006982:Hypertonic Solutions / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins; D009392:Nephrectomy; D009395:Nephritis, Interstitial / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014867:Water / Q000494:pharmacology*
D002352:Carrier Proteins; D018076:DNA, Complementary; D005353:Fibronectins; D006360:Heat-Shock Proteins; D006982:Hypertonic Solutions; D008565:Membrane Proteins; D012333:RNA, Messenger; D027981:Symporters; D016212:Transforming Growth Factor beta; D014867:Water; C073884:SLC5A3 protein, human