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Feng, Fanchao; Wang, Zhichao; Li, Ruofei; Wu, Qi; Gu, Cheng; Xu, Yong; Peng, Wenpan; Han, Di; Zhou, Xianmei; Wu, Jing; He, Hailang
Biomedicine & pharmacotherapy, 04/2019, Letnik: 112Journal Article
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease with a poor prognosis and limited treatment options. The incidence of IPF increases with age, and the mechanisms related to aging such as cellular senescence have been strongly implicated in disease pathology. Therefore, a better understanding of fibroblasts senescence might provide a new therapeutic strategy to prevent and treat pulmonary fibrosis. In this study, we aimed to explore the effects of citrus alkaline extracts (CAE) on the fibroblasts senescence, and elucidate the underlying mechanism to ameliorate pulmonary fibrosis. We demonstrated that CAE mitigated the collagen deposition by the initial early treatment, suggesting a potential preventive effect of CAE on pulmonary fibrosis. The expression of senescence biomarkers P16INK4a 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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