| Bioactivity of glomerular ultrafiltrate during heavy proteinuria may contribute to renal tubulo-interstitial lesions: evidence for a role for insulin-like growth factor I. | |
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MedLine Citation:
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PMID: 8690782 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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R Hirschberg |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 98 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 1996 Jul |
Date Detail:
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Created Date: 1996-08-26 Completed Date: 1996-08-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 116-24 Citation Subset: AIM; IM |
Affiliation:
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Division of Nephrology & Hypertension, Harbor-UCLA Medical Center, Torrance, California 90509, USA. hirschberg@afp76.hume.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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
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