Osteogenic Protein-1: gene expression and treatment in rat remnant kidney model.
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-I (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 microg/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 epithelialhyperplasia) 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.
Department of Nephrology, Miami Children's Hospital, Miami, Florida, USA.
Philip H
PH
Dube
Maria M
MM
Almanzar
Kendall S
KS
Frazier
William K
WK
Jones
Marc F
MF
Charette
Ana
A
Paredes
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000473:pathology; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta