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Published ahead of print on January 19, 2006, doi:10.1165/rcmb.2005-0252OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 5, May 2006, 625-633

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Submitted on July 8, 2005
Revised on January 17, 2006

Telomerase Regulation of Myofibroblast Differentiation

Tianju Liu1, Biao Hu1, Myoung Ja Chung1, Matt Ullenbruch1, Hong Jin1, and Sem H Phan1*

1 Department of Pathology, University of Michigan, Ann Arbor, MI, USA

* To whom correspondence should be addressed. E-mail: shphan{at}umich.edu.

Telomerase activity is induced in lung proliferating fibroblasts, besides its wide expression in cancerous cells. It is preferentially expressed in fibroblasts vs. myofibroblasts. However, it is unknown whether regulation of telomerase expression is related to the process of fibroblast differentiation into myofibroblast. The objective of this study was to clarify such a potential link between telomerase expression and myofibroblast differentiation. Telomerase inhibitor, 3'-azido-2', 3'-dideoxythymidine (AZT) or antisense oligonucleotide to the telomerase RNA component was used to inhibit the induced fibroblast telomerase activity. The results showed that inhibition of induced telomerase increased {alpha}-smooth muscle actin ({alpha}-SMA) expression, an indicator of myofibroblast differentiation. In contrast, induction of telomerase by bFGF inhibited {alpha}-SMA expression. These findings suggest that the loss of telomerase activity is closely associated with myofibroblast differentiation, and possibly functions as a potential trigger for myofibroblast differentiation. Conversely, expression of telomerase suppresses myofibroblast differentiation.




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