Osteogenic Protein-1: Gene Expression and Treatment in the 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.