Document Detail


Bioactivity of glomerular ultrafiltrate during heavy proteinuria may contribute to renal tubulo-interstitial lesions: evidence for a role for insulin-like growth factor I.
MedLine Citation:
PMID:  8690782     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clinical and experimental data have indicated that heavy proteinuria in renal glomerular diseases is associated with the formation of tubulo-interstitial fibrosis and contributes to the progression of renal failure. Albumin in glomerular ultrafiltrate does not appear to cause this sequelae, rather than compounds that are associated with ultrafiltered plasma proteins. One such protein-bound factor could be insulin-like growth factor I (IGF-I). The present studies show that in nephrotic rats, IGF-I is ultrafiltered in conjunction with IGF-binding protein-2 and is present in proximal tubular fluid at 1.35 nM. Proximal tubular fluid from nephrotic rats autophosphorylates IGF-I receptors in cultured proximal tubular cells. Nephrotic, but not control, rat proximal tubular fluid increases the [3H]thymidine incorporation in cultured tubular cells, and neutralizing IGF-I-receptor antibodies partially inhibit this activity. Incubation of cultured proximal tubular cells with an extract that was prepared from nephrotic rat urine increases the secretion of collagen types I and IV. Secretion of the two collagens is in part ameliorated by neutralizing IGF-I-receptor antibody. In concert, these findings suggest that the IGF-I present in nephrotic rat tubular fluid is bioactive and may contribute to the development of tubulo-interstitial fibrosis in chronic nephrotic glomerular diseases.
Authors:
R Hirschberg
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  98     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-08-26     Completed Date:  1996-08-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  116-24     Citation Subset:  AIM; IM    
Affiliation:
Division of Nephrology & Hypertension, Harbor-UCLA Medical Center, Torrance, California 90509, USA. hirschberg@afp76.hume.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Collagen / secretion
Fibrosis / etiology
Filtration
Glomerular Filtration Rate
Hemodynamics
Insulin-Like Growth Factor I / metabolism
Kidney Glomerulus / metabolism*
Kidney Tubules / pathology*
Male
Mice
Nephrotic Syndrome / complications*
Proteinuria / complications*
Rats
Rats, Wistar
Receptor, IGF Type 1 / metabolism
Urine / chemistry
Chemical
Reg. No./Substance:
67763-96-6/Insulin-Like Growth Factor I; 9007-34-5/Collagen; EC 2.7.10.1/Receptor, IGF Type 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Intracellular lactate- and pyruvate-interconversion rates are increased in muscle tissue of non-insu...
Next Document:  Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed an...