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In vitro liver tissue model established from transgenic mice: role of HIF-1alpha on hypoxic gene expression.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Allen, Jared W. Khetani, Salman R. Johnson, Randall S. Bhatia, Sangeeta N. |
| Copyright Year | 2006 |
| Abstract | The instability of the hepatocyte phenotype in vitro has limited the ability to quantitatively investigate regulation of stress responses of the liver. Here, we adopt a tissue-engineering approach to form stable liver tissue in vitro by forming collagen "sandwich" cultures of transgenic murine hepatocytes harboring a regulatory gene of interest flanked by loxP sites. The floxed gene is excised in a subset of cultures by transfection with adenovirus carrying the gene for Cre-recombinase, thereby generating wild-type and null liver tissues from a single animal. In this study, we specifically investigated the role of hypoxia inducible factor 1 alpha (HIF-1alpha) in the hepatocellular response to hypoxia. Using high-density oligonucleotide arrays, we examined genome-wide gene expression after 8 h of hypoxia in wild-type and HIF- 1alpha null hepatocyte cultures. We identified more than 130 genes differentially expressed under hypoxia involved in metabolic adaptation, angiogenic signaling, immediate early response, and cell cycle regulation. Real-time polymerase chain reaction analysis verified that known hypoxia-responsive genes such as glucose transporter-1 and vascular endothelial growth factor were induced in a HIF-1alpha-dependent manner under hypoxia. Our results demonstrate the potential to integrate in vitro tissue models with transgenic and microarray technologies for the study of physiologic stress responses. |
| File Format | PDF HTM / HTML |
| DOI | 10.1089/ten.2006.12.3135 |
| PubMed reference number | 17518628 |
| Journal | Medline |
| Volume Number | 12 |
| Issue Number | 11 |
| Alternate Webpage(s) | http://projects-web.engr.colostate.edu/mTm_Khetani/wp-content/uploads/2014/01/2006_IVLTMEFTMRHHGE.pdf |
| Alternate Webpage(s) | http://lmrt.mit.edu/sites/default/files/Allen2006_TissEng.pdf |
| Alternate Webpage(s) | http://lmrt.mit.edu/publications/2006/Allen2006_TissEng.pdf |
| Alternate Webpage(s) | https://doi.org/10.1089/ten.2006.12.3135 |
| Journal | Tissue engineering |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
