Journal article
H. Sirma, Mukesh Kumar, Jitendra Kumar Meena, B. Witt, J. Weise, A. Lechel, Satyanarayana Ande, V. Sakk, C. Guguen-Guillouzo, L. Zender, K. Rudolph, C. Günes
Gastroenterology, 2011
Gastroenterology, 2011
Semantic Scholar
DOI
PubMed
Cite
Cite
APA
Click to copy
Sirma, H., Kumar, M., Meena, J. K., Witt, B., Weise, J., Lechel, A., … Günes, C. (2011). The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation. Gastroenterology.
Chicago/Turabian
Click to copy
Sirma, H., Mukesh Kumar, Jitendra Kumar Meena, B. Witt, J. Weise, A. Lechel, Satyanarayana Ande, et al. “The Promoter of Human Telomerase Reverse Transcriptase Is Activated during Liver Regeneration and Hepatocyte Proliferation.” Gastroenterology (2011).
MLA
Click to copy
Sirma, H., et al. “The Promoter of Human Telomerase Reverse Transcriptase Is Activated during Liver Regeneration and Hepatocyte Proliferation.” Gastroenterology, 2011.
BibTeX Click to copy
@article{h2011a,
title = {The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation.},
year = {2011},
journal = {Gastroenterology},
author = {Sirma, H. and Kumar, Mukesh and Meena, Jitendra Kumar and Witt, B. and Weise, J. and Lechel, A. and Ande, Satyanarayana and Sakk, V. and Guguen-Guillouzo, C. and Zender, L. and Rudolph, K. and Günes, C.}
}
Abstract
BACKGROUND & AIMS Telomerase activity has not been detected in healthy human liver biopsy samples, but it is up-regulated in most human liver tumors. It is not clear whether telomerase is activated in response to acute or chronic liver injury. Telomerase activity is closely associated with expression of its catalytic subunit, telomerase reverse transcriptase (TERT). We analyzed the activity of the human TERT (hTERT) promoter during liver regeneration in vivo and hepatocyte proliferation in vitro.
METHODS We used hTERTp-lacZ transgenic mice, which contain an 8.0-kilobase pair fragment of the hTERT gene promoter, to study the role of TERT in liver regeneration following partial hepatectomy. As an in vitro model, we used the HepaRG cell line as a new model system for human hepatocyte proliferation and differentiation.
RESULTS Activity of the hTERT promoter increased significantly after partial hepatectomy; it was also induced in hepatocytes, based on immunohistologic analysis. Similar to the in vivo results, telomerase activity and hTERT expression were up-regulated in proliferating HepaRG cells and repressed in response to growth arrest and differentiation. Promoter mapping revealed that a proximal 0.3-kilobase pair fragment contains all elements necessary for regulation of hTERT in HepaRG cells. We identified E2F2 and E2F7 as transcription factors that control the differential expression of hTERT in proliferating hepatocytes, in vitro and in vivo.
CONCLUSIONS hTERT is induced in hepatocytes during liver regeneration, indicating a functional role for telomerase in human liver.
