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Telomerase Regulation of Myofibroblast Differentiation

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to Sem H. Phan, 1150 W. Medical Center Dr., Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109. E-mail: shphan{at}umich.edu

Telomerase activity, which has wide expression in cancerous cells, is induced in lung proliferating fibroblasts. It is preferentially expressed in fibroblasts versus myofibroblasts. It is unknown whether regulation of telomerase expression is related to the process of fibroblast differentiation into myofibroblasts. 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, 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 -smooth muscle actin expression, an indicator of myofibroblast differentiation. In contrast, induction of telomerase by basic fibroblast growth factor inhibited -smooth muscle actin expression. These findings suggest that the loss of telomerase activity is closely associated with myofibroblast differentiation and possibly functions as a trigger for myofibroblast differentiation. Conversely, expression of telomerase suppresses myofibroblast differentiation.

Key Words: cell differentiation • fibroblast • -smooth muscle actin • telomerase reverse transcriptase

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