Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Free Full Text (Free PDF) Free
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Dube, P. H.
Right arrow Articles by Paredes, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dube, P. H.
Right arrow Articles by Paredes, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

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

Philip H. Dube

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.

Toxicologic Pathology, Vol. 32, No. 4, 384-392 (2004)
DOI: 10.1080/01926230490440925
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?