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Aim To study the effects of pyrin recombi-nant protein ( PRP ) on VEGF/VEGFR2/ MMP-9 sig-naling pathway in bleomycin-induced pulmonary fibro-sis of rats. Methods Sixty male Wistar rats were ran-domly divided into groups of control ( n=10 ) , model ( n=20 ) , PRP ( n=20 ) , and SU5416 ( n=10 ) . All the rats, except for those in control group, were estab-lished as the model of interstitial pulmonary fibrosis by perfusion of bleomycin (5 mg·kg-1 ) through tracheal intubation. From the second day after modeling, all rats were intragastrically administered with drugs or sa-line, according to different groups designed. The rats were sacrificed on the 14th and 28th day, and lung samples were taken out. The pathological changes of interstitial pulmonary fibrosis were observed by HE staining and Masson staining to evaluate the degree of alveolitis and pulmonary fibrosis. Expressions of VEGF, VEGFR2, MMP-9 protein and mRNA were de-tected by immunohistochemistry and RT-PCR. Results On the 14th and 28th day, the alveolitis, pulmonary fibrosis, expression of VEGF, VEGFR2, MMP-9 and mRNA increased significantly in the model group com-pared with in the control group ( P <0. 05 ) , and de-creased significantly in PRP group than those in the model group ( P <0. 05 ) . Conclusion PRP plays a role of anti-pulmonary fibrosis via the down-regulation of VEGF/VEGFR2/MMP-9 signaling pathway.
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Objective To explore the effect of p21Waf1/Cip1 methylation changes on the process of cellular senescence .Methods Bisulfite sequencing was used to analyze the methylation changes of p21Waf1/Cip1 in the process of cellular senescence;p21Waf1/Cip1 ex‐pression was detected by RT‐PCR and Western‐blot ;Middle‐aged 2BS cells was treated by 5‐aza‐CdR and cellular senescence was detected by MTT and SA‐β‐Gal staining .Results Bisulfite sequencing analysis of p21Waf1/Cip1 promoter showed that CpGs were methylated by 1 .25% in the young 2BS cells ,by 27 .27% in the middle‐aged 2BS cells ,while only by 0 .64% in the senescent cells . The expression of p21Waf1/Cip1 was low in the young(28 PD) 2BS cells ,it increased first(35 PD) but decreased later in the middle‐aged(42 PD) cells .In the senescent 2BS cells ,p21Waf1/Cip1 expression was further increased .5‐aza‐CdR treatment resulted in de‐creased growth rate but increasedβ‐Gal staining of middle‐aged 2BS cells .Conclusion The process of cellular senescence is regula‐ted by the status of p21Waf1/Cip1 methylation ,and p21Waf1/Cip1 demethylation accelerates cellular senescence .