| Info. | Vol.9 - No.3 (2015.09.20) |
|---|---|
| Title | Comparative Gene Expression Analysis in the Liver, Kidney and Blood Vessels during Renal Injury after Repeated Exposure to Tacrolimus in Sprague-Dawley Rats |
| Authors | Sun Mi Hwang1, Se-Myo Park1, Ji-Seong Jeong1, Kyoung-Sik Moon1, Yong-Bum Kim1, Seokjoo Yoon1,2,* & Jung-Hwa Oh1,2,* |
| Institutions | 1Korea Institute of Toxicology (KIT), 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343, Korea 2Department of human and environmental toxicology, University of Science & Technology, Daejeon 305-350, Korea |
| Abstract | To elucidate the molecular mechanisms associated with renal injury based on multi-organ interactions, we simultaneously examined the changes in expression profiles of the liver, kidneys, and blood vessels after treatment with the nephrotoxic drug tacrolimus. Sprague-Dawley rats were treated daily with tacrolimus and sacrificed 28 d after oral administration. Serum biochemistry analysis of the major injury markers was performed. Histopathological characteristics were also observed. Total RNA was extracted from the liver, kidneys, and blood vessels from the thoracic aorta, followed by microarray analysis. Differentially expressed genes were selected based on 1.5-fold changes and statistical significance (P<0.05). The effects of three dosages of tacrolimus on transcription levels were analyzed within and among the three organs. Gene functions, as well as the biological and toxicological functions of the differentially regulated genes, were analyzed using Ingenuity Pathways Analysis (IPA). IPA identified genes involved in metabolic activation, including lipid metabolism, renal tubule injury, and cell proliferation in tacrolimus-treated livers, kidneys, and blood vessels, respectively. In response to tacrolimus treatment, genes related to lipid metabolic responses were regulated in the three organs similarly. Genes associated with inflammatory response were regulated in the liver and kidneys similarly. Based on the results from this study, we suggest the molecular pathways involved in the response to tacrolimus in multiple organs. We also provide information about candidate genes, to evaluate the toxicity induced by tacrolimus. These results might be helpful to elucidate the underlying mechanisms of nephrotoxicity by interaction among multiple organs. |
| Keyword | Tacrolimus, Multiple organs interaction, Kidney toxicity, Nephrotoxicity, Liver, Blood vessel, Gene expression profiling |
| PDF File |
 # 2010년도 발행분 부터는 Springer 의 BioChip Journal 페이지에서 전문을 열람하실 수 있습니다.
# 학회회원 로그인 후 [ Springer BioChip Journal 열람하기 ] 버튼을 클릭하시면 새창으로 열립니다. |
