Agnieszka Gadecka et al.
Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS exhibited significantly higher levels of CLDN1 expression exclusively in SIPS. Moreover, nuclear accumulation of this protein was also characteristic only of prematurely senescent cells. ChIP-seq results suggest that higher CLDN1 expression in SIPS might be a result of a more open chromatin state, as evidenced by a broader H3K4me3 peak in the gene promoter region. However, the broad H3K4me3 peak and relatively high CLDN1 expression in RS did not translate into protein level, which implies a different regulatory mechanism in this type of senescence. Elevated CLDN1 levels were also observed in VSMCs isolated from atherosclerotic plaques, although this was highly donor dependent. These findings indicate that increased CLDN1 level in prematurely senescent cells may serve as a promising cell-specific marker of SIPS in VSMCs, both in vitro and ex vivo.
