Citrus alkaline extracts prevent fibroblast senescence to ameliorate pulmonary fibrosis via activation of COX-2

Abstract

and P21, concomitant with down-regulation of the myofibroblasts marker α-SMA, and the number of senescence-associated β-galactosidase (SA-β-Gal) positive cells were decreased by CAE treatment, indicating a significant inhibitory effect of CAE on fibroblast senescence. Additionally, CAE down-regulated the expression of the senescence-associated secretory phenotype (SASP) in etoposide-induced senescent fibroblasts. Further studies indicated that COX-2 activation was required for CAE to inhibit the lung fibroblast senescence through a P53-dependent pathway. Results showed that the anti-senescence effect of CAE was abrogated when COX-2 was knocked down or inhibited by COX-2 inhibitor NS-398 or indomethacin in lung fibroblasts. Meanwhile, the anti-fibrotic and anti-senescence effect of CAE were abolished due to disruption of COX-2 in vivo. Collectively, our results provided a novel insight into the potential mechanism of CAE to inhibit the fibroblasts activation through preventing cellular senescence.