In vitro gene regulatory networks predict in vivo function of liver

BMC Systems Biology

Edward J Perkins²  Junmei Ai¹  Choo Y Ang³  Xin Guan³  David R Johnson²  Youping Deng⁴ 

[1] School of Computing, University of Southern Mississippi, Hattiesburg, MS 39406, USA;US Army Engineer Research and Development Center, 3909 Halls Ferry Road, Vicksburg, MS 39180, USA;SpecPro Inc., Vicksburg, MS 39180, USA;Rush University Cancer Center, Rush University Medical Center, Chicago, IL 60612, USA

Others  :  1216734
DOI  :  10.1186/1752-0509-4-153

 received in 2010-06-29, accepted in 2010-11-12,  发布年份 2010

【 摘 要 】

Background

Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed.

Results

Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo.

Conclusions

The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity.

【 授权许可】

   
2010 Deng et al; licensee BioMed Central Ltd.

【 图 表 】

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