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Osteogenic Protein-1: Gene Expression and Treatment in the Rat Remnant Kidney Model

Division of Nephrology, Miami Children's Hospital, Miami, Florida

Maria M. Almanzar

Division of Nephrology, Miami Children's Hospital, Miami, Florida

Kendall S. Frazier

Department of Veterinary Pathology, College of Veterinary Medicine, University of Georgia, Tifton, Georgia

William K. Jones

Curis, Inc., Cambridge, Massachusetts

Marc F. Charette

Curis, Inc., Cambridge, Massachusetts

Ana Paredes

Division of Nephrology, Miami Children's Hospital, Miami, Florida, ana.paredes{at}mch.com

Osteogenic Protein-1 (OP-1) is a bone morphogen involved in tissue repair and development. We have shown that OP-1 is downregulated during acute ischemic renal injury. Here we report the use of the rat remnant kidney model (RRKM) to evaluate changes in kidney OP-1 expression during chronic injury, and determine if treatment with recombinant human OP-1 (rhOP-1) aids in recovery from injury. Sprague—Dawley rats were subjected to kidney decapsulation (Cx) or 5/6 nephrectomy (Nx). Serum for BUN and creatinine and tissue for histology and mRNA analysis were collected at: 2, 10, and 12—14 wks post Nx. We show kidney OP-1 mRNA levels were downregulated at 2 and 12—14 wks post Nx. To determine the effect of rhOP-1 in the RRKM, rhOP-1 (0.25, 2.5 or 25 µg/kg) or vehicle (V) was injected in a second set of rats, 2 weeks after 2/3 left Nx for a total of six doses. Nx rats treated with rhOP-1 showed significantly increased tubular regeneration (increased mitotic figures, polyoid infolding, and tubular epithelial hyperplasia) in a dose dependent manner without changes in glomerular or tubular damage. rhOP-1 stimulates tubular epithelial cell regeneration, early in the repair process in a chronic renal failure model, before significant fibrosis is established.

Key Words: Osteogenic Protein-1 • bone morphogenetic protein-7 • chronic renal failure • tubular regeneration • rat remnant kidney model.

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Toxicologic Pathology, Vol. 32, No. 4, 384-392 (2004)
DOI: 10.1080/01926230490440925


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Dube, P. H. Articles by Paredes, A. Search for Related Content PubMed PubMed Citation Articles by Dube, P. H. Articles by Paredes, A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Social Bookmarking                         What's this?