Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-5-13
pubmed:abstractText
Diabetic nephropathy is characterized by renal hypertrophy, thickening of basement membranes, and accumulation of extracellular matrix in the glomerular mesangium and the interstitium. Our previous investigations have shown that high glucose concentration increases transforming growth factor (TGF)-beta1 mRNA in mesangial and proximal tubule cells and that treatment with anti-TGF-beta antibody results in prevention of the effects of high glucose on cell growth (e.g., induction of cellular hypertrophy) and the stimulation of collagen biosynthesis. We evaluated in vivo the functional role of the renal TGF-beta system in diabetic kidney disease by treatment of streptozotocin-induced diabetic mice with either a neutralizing monoclonal antibody against TGF-beta1, -beta2, and -beta3 (alphaT) or nonimmune murine IgG for 9 days. Diabetic mice given IgG demonstrated total kidney and glomerular hypertrophy, significantly elevated urinary TGF-beta1 protein, and increased mRNAs encoding TGF-beta1, type II TGF-beta receptor, alpha1(IV) collagen, and fibronectin. Treatment of diabetic mice with alphaT prevented glomerular hypertrophy, reduced the increment in kidney weight by approximately 50%, and significantly attenuated the increase in mRNA levels without having any effect on blood glucose. The antibody was without significant effect on mRNA levels in nondiabetic mice. This is the first demonstration that the early characteristic features of diabetic renal involvement, which include hypertrophy and increased matrix mRNAs, are largely mediated by increased endogenous TGF-beta activity in the kidney and that they can be significantly attenuated by treatment with neutralizing anti-TGF-beta antibodies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
522-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8603776-Animals, pubmed-meshheading:8603776-Antibodies, Monoclonal, pubmed-meshheading:8603776-Body Weight, pubmed-meshheading:8603776-DNA, Complementary, pubmed-meshheading:8603776-Diabetes Mellitus, Experimental, pubmed-meshheading:8603776-Diabetic Nephropathies, pubmed-meshheading:8603776-Extracellular Matrix Proteins, pubmed-meshheading:8603776-Female, pubmed-meshheading:8603776-Gene Expression, pubmed-meshheading:8603776-Hypertrophy, pubmed-meshheading:8603776-Immunoglobulin G, pubmed-meshheading:8603776-Kidney, pubmed-meshheading:8603776-Kidney Cortex, pubmed-meshheading:8603776-Mice, pubmed-meshheading:8603776-Mice, Inbred C57BL, pubmed-meshheading:8603776-Neutralization Tests, pubmed-meshheading:8603776-Organ Size, pubmed-meshheading:8603776-Reference Values, pubmed-meshheading:8603776-Time Factors, pubmed-meshheading:8603776-Transforming Growth Factor beta
pubmed:year
1996
pubmed:articleTitle
Neutralization of TGF-beta by anti-TGF-beta antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice.
pubmed:affiliation
Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't