The Dual Distinct Role of Telomerase in Repression of Senescence and Myofibroblast Differentiation

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 and 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 expression had no effect on expression. Both TERT and YB-1 were shown to bind the promoter but only YB-1 was shown to bind the ACTA2 promoter. TERT overexpression inhibited promoter activity while stimulating YB-1 expression and activation to repress gene. TERT repressed myofibroblast differentiation and senescence via distinct mechanisms. The latter was associated with TERT binding to the promoter, but not to the promoter, which may require interaction with co-factors such as YB-1.