POSTER ABSTRACT / DETAILS:
To elucidate the molecular mechanisms associated with renal injury based on target organ interactions, we examined simultaneously the changes in expression profiles of liver, kidney, and the blood vessels after three nephrotoxicants including cyclosporin A (CsA), tacrolimus (FK506) and cyclophosphamide (CPM). Spraugue-Dawley rats were treated daily with CsA, FK506, and CPM and then sacrificed at 1, 7, and 28 day after oral administration.
Serum biochemistry for major injury markers and histopathological observation were also performed. Total RNAs were extracted from the liver, the kidney, and the thoracic aorta and then microarray analysis were performed. Differentially expressed genes were selected based on fold changes and significance and commonly expressed genes were compared among three target organs.
The effects of three nephrotoxicants were also compared under each each target organ. Gene functions were analyzed using Ingenuity Pathways Analysis (IPA) and biological and toxicological function of significantly regulated genes showed that genes involved in metabolic activation, renal tubule injury, and endothelial cell proliferations in nephrotoxicants-treated group in the liver, the kidney, and the aorta, respectively. In CPM-treated group, inflammatory response related genes were commonly regulated in all target organs.
Several genes expressed in dose dependent manner were selected the mRNA levels were validated by real time PCR.
Here we suggests molecular pathways in the target organs in response to nephrotoxicants and also provide the information about candidate genes which can evaluate the toxicity induced by nephrotoxicants. These results may be helpful to elucidate underlying mechanism of target organ interaction during nephrotoxicity.