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Regulation Of LncRNA-TERRA On Telomere In AECs-? Of Idiopathic Pulmonary Fibrosis

Posted on:2016-09-10Degree:MasterType:Thesis
Country:ChinaCandidate:C P MaoFull Text:PDF
GTID:2334330488999241Subject:Immunology
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Objective:The pathogenesis of idiopathic pulmonary fibrosis is still not clear and lack of effective treatment measures. Oxidative damage has important role in IPF. AECs-? damage/apoptosis is an important event initial formation of pulmonary fibrosis. IPF is a tapicaly elderly desesis. The length of the telomeres was closely related with aging. With the continuous replication of chromosomes, Telomeres become shorter. When it reduced to the critical value, telomeres cannot protect chromosome. Then, cell division stops, cells were apoptosis. The length of the telomeres was maintained by telomerase. LncRNA-TERRA could inhibit telomerase activity. In this study, we investigate the regulation of Lnc-RNA in order to provide targets for the treatment of IPF.Methods:A549 indued by H2O2 to establish the oxidative damage models of IPF, the transdifferentiation models were constructed by TGF-? induce A549 or HLF. The levels of LncRNA-LncRNA-TERRA in IPF patients and changes ofcell models were detected by real-time PCR. The levels of LncRNA-TERRA were silence by siRNA-TERRA1 or siRNA-TERRA2. Flow cytometry acquire the rate of cell apoptosis. Real-time PCR detect the expression of p53, bax and bcl-2. CCK-8 was used to acquire the rate of cell proliferation. The kit telomerase activity was detected the telomerase activity in real time. The expression of TERT, PCNA, and cyclin D1/E was detected by western blot.Results:The level of LncRNA-TERRA increased in IPF. SiRNA-TERRA1/2 decreases the AECs-? apoptosis and the levels of p53 and bax. Down-regulation LncRNA-TERRA can raise the AECs-? proliferation and the expression of PCNA. SiRNA-TERRA1/2 promotes the expression of cyclin D1/E. Down-regulation LncRNA-TERRA increase telomerase activity and the level of TERT.Conclusion:LncRNA-TERRA regulates the lengh of telomeres by inhibiting telomerase activity, decrease cell regeneration ability, cause the occurrence of IPF.
Keywords/Search Tags:IPF, LncRNA-TERRA, telomeres, oxidative damage, transdifferentiation
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