Research Paper Volume 13, Issue 13 pp 16957—16973
The dual distinct role of telomerase in repression of senescence and myofibroblast differentiation
- 1 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- 2 Department of Respiratory Medicine, Fujieda Municipal General Hospital, Fujieda, Japan
- 3 Xinjiang Key Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
Received: January 27, 2021 Accepted: June 4, 2021 Published: July 12, 2021https://doi.org/10.18632/aging.203246
How to Cite
Copyright: © 2021 Harada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Many aging related diseases such as cancer implicate the myofibroblast in disease progression. Furthermore genesis of the myofibroblast is associated with manifestation of cellular senescence of unclear significance. In this study we investigated the role of a common regulator, namely telomerase reverse transcriptase (TERT), in order to evaluate the potential significance of this association between both processes. We analyzed the effects of TERT overexpression or deficiency on expression of CDKN2A and ACTA2 as indicators of senescence and differentiation, respectively. We assess binding of TERT or YB-1, a repressor of both genes, to their promoters. TERT repressed both CDKN2A and ACTA2 expression, and abolished stress-induced expression of both genes. Conversely, TERT deficiency enhanced their expression. Altering CDKN2A expression had no effect on ACTA2 expression. Both TERT and YB-1 were shown to bind the CDKN2A promoter but only YB-1 was shown to bind the ACTA2 promoter. TERT overexpression inhibited CDKN2A promoter activity while stimulating YB-1 expression and activation to repress ACTA2 gene. TERT repressed myofibroblast differentiation and senescence via distinct mechanisms. The latter was associated with TERT binding to the CDKN2A promoter, but not to the ACTA2 promoter, which may require interaction with co-factors such as YB-1.