PMID- 8023968
OWN - NLM
STAT- MEDLINE
DCOM- 19940802
LR  - 20180109
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 266
IP  - 6 Pt 2
DP  - 1994 Jun
TI  - Protein restriction reduces transforming growth factor-beta and interstitial 
      fibrosis in nephrotic syndrome.
PG  - F884-93
AB  - Nephrotic syndrome induced by puromycin aminonucleoside (PAN) is characterized by 
      tubulointerstitial (TI) inflammation, foci of TI fibrosis, and increased renal 
      mRNA levels for matrix genes, the tissue inhibitor of metalloproteinases (TIMP), 
      and the transforming growth factor-beta 1 (TGF-beta 1). To investigate the 
      ability of a low-protein diet known to decrease TI inflammation to alter the 
      degree of renal fibrosis, we studied four groups of rats: 27% protein PAN, 27% 
      protein control, 8% protein PAN, and 8% protein control. Renal TGF-beta 1 mRNA 
      levels correlated with the number of interstitial macrophages (r = 0.76) and were 
      significantly reduced by dietary protein restriction. On day 10, Northern blot 
      analysis showed that the elevated renal mRNA levels for procollagens alpha 1 (I), 
      alpha 1(III), and alpha 2(IV) and fibronectin in the PAN-treated rats were 
      significantly reduced by 8% dietary protein. In contrast, genes regulating matrix 
      degradation (stromelysin and TIMP) were relatively unchanged by the low-protein 
      diet. The number of foci of interstitial fibrosis and total renal collagen were 
      greater in the PAN + 27% protein group than in the control groups. Both 
      parameters of fibrosis were partially normalized in the PAN + 8% protein group. 
      The results of this study suggest that dietary protein restriction attenuates TI 
      fibrosis in PAN-induced nephrosis by partially reversing the increase in renal 
      matrix synthesis. This effect was associated with decreased renal expression of 
      the fibrogenic cytokine TGF-beta 1, which may be partially mediated by the 
      concomitant reduction in the number of interstitial inflammatory macrophages.
FAU - Eddy, A A
AU  - Eddy AA
AD  - Department of Pediatrics, Hospital for Sick Children, University of Toronto, 
      Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Dietary Proteins)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Cholesterol/blood
MH  - Dietary Proteins/*administration & dosage/pharmacology
MH  - Extracellular Matrix Proteins/genetics/metabolism
MH  - Female
MH  - Fibrosis
MH  - Kidney/metabolism/pathology
MH  - Nephritis/pathology
MH  - Nephrotic Syndrome/*metabolism/*pathology
MH  - Proteinuria/urine
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Transforming Growth Factor beta/*metabolism
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
AID - 10.1152/ajprenal.1994.266.6.F884 [doi]
PST - ppublish
SO  - Am J Physiol. 1994 Jun;266(6 Pt 2):F884-93. doi: 
      10.1152/ajprenal.1994.266.6.F884.