Regulation Mechanisms Of LncITPE In Idiopathic Pulmonary Fibrosis

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating interstitial lung disease and seriously harmful to human health. Until now, IPF remains a disease with no clinical application of molecular markers can shed light on its molecular mechanisms. And it is great difficulty for susceptibility analysis, diagnosis, especially for early diagnosis, treatment and prognosis. With the discovery and the function of non-coding RNA research, their roles in mammalian evolution and disease get more and more attention, and it is an important drug target and molecular therapy for human diseases. In this study, with the early stage of chip results, we choose IncITPF which was significantly higher in rat model of pulmonary fibrosis, explore its expression,function and mechanism in the development of IPF, and provide new molecular targets for IPF treatment.Methods: Bleomycin (BLM) induced lung fibrosis in rats and TGF-?1 induced transdifferentiation of AECs-? in RLE-6TN and A549 cells. The IncITPF expression was detected by qRT-PCR in vivo and in vitro models. The IncITPF expression in IPF patients' whole blood was also detected by qRT-PCR. The levels of IncITPF were silenced by siRNA or IncRNA Smart Silencer. Immunofluorescence observes the expression of a-SMA and western blot detectes the protein level of E-cadherin, SP-C,a-SMA and Snail. Transwell experiments and Real Time Cellular Analysis (RTCA)detect the migration ability of transdifferentiated RLE-6TN and A549 cells with or without transfection. CHIP-PCR explore the regulation of IncITPF to ITGBL1 gene promoter region' histones.Results: LncITPF was upregulated in vivo and in vitro idiopathic pulmonary fibrosis models, and expressed at higher levels in IPF patients' whole blood. LncITPF can promote epithelial-mesenchymal transition (EMT) and enhance myofibroblast migration ability. SiRNA and IncRNA Smart Silencer both knockdown the expression of IncITPF in cells, and increase the protein level of E-cadherin and SP-C. While the protein level of a-SMA and Snail and the migration of myofibroblast were decreased after transfection. LncITPF higher expression promotes the level of histone H3 and H4 acetylation in ITGBL1 promoter region. And IncRNA Smart Silencer can decrease the content of histone H3, H4 acetylation in ITGBL1 promoter region.Conclusion: LncITPF can promote the level of histone H3 and H4 acetylation in ITGBL1 promoter region, thereby increasing the expression of ITGBL1, mediate the EMT phenomenon and enhance myofibroblast migration ability,thus promote the development of IPF.