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Abstract：
BACKGROUND: Cigarette smoking may impact the progression of idiopathic pulmonary fibrosis (IPF), and the intensity of smoking presents a dose-response association with IPF.
METHODS: We retrospectively analyzed IPF patients diagnosed in our hospital from 2014 to 2018 and performed follow-up to confirm survival status and duration, and determine the effect of smoking on the prognosis of IPF. We retrieved information on IPF from a bioinformatics database to identify the differential expression of lncRNAs and proteins in smokers. Therefore, we explored and verified the mechanism by which cigarette smoke exposure (CSE) regulates LINC00665/XBP-1 involvement in pulmonary fibrosis through cell experiments. We clarified the mechanism between LINC00665 and XBP-1 through cellular and molecular experiments, and verified the inhibitory effect of silencing LINC00665 on pulmonary fibrosis by using a bleomycin (BLM)-induced pulmonary fibrosis model.
RESULTS: We found that smokers with IPF had a poor prognosis compared with non-smokers. Both the expression of LINC00665 and XBP-1 in IPF lung tissue and smoker lung tissue were significantly upregulated, moreover, LINC00665 was higher in smoker IPF lung tissue than in smoker healthy people. Exposure to CSE could upregulate LINC00665/XBP-1 in lung fibroblast-to-myofibroblast transition. Cellular and molecular experiments showed that LINC00665 regulates the expression of XBP-1 by targeting miR-214-3p. LINC00665 expression, was significantly upregulated in BLM-induced mouse lung fibrosis tissues, and LINC00665 knockdown inhibited fibrogenesis in BLM-induced lung fibrosis.
CONCLUSIONS: Our study found that the high expression of LINC00665 is involved in the pathogenesis of smoker IPF and that CSE may positively regulate LINC00665/XBP-1 to participate in lung fibroblast-to-myofibroblast transition. These findings help elucidate the pathogenesis of smoker IPF and may contribute to the development of new targeted drugs for IPF therapy.
METHODS: We retrospectively analyzed IPF patients diagnosed in our hospital from 2014 to 2018 and performed follow-up to confirm survival status and duration, and determine the effect of smoking on the prognosis of IPF. We retrieved information on IPF from a bioinformatics database to identify the differential expression of lncRNAs and proteins in smokers. Therefore, we explored and verified the mechanism by which cigarette smoke exposure (CSE) regulates LINC00665/XBP-1 involvement in pulmonary fibrosis through cell experiments. We clarified the mechanism between LINC00665 and XBP-1 through cellular and molecular experiments, and verified the inhibitory effect of silencing LINC00665 on pulmonary fibrosis by using a bleomycin (BLM)-induced pulmonary fibrosis model.
RESULTS: We found that smokers with IPF had a poor prognosis compared with non-smokers. Both the expression of LINC00665 and XBP-1 in IPF lung tissue and smoker lung tissue were significantly upregulated, moreover, LINC00665 was higher in smoker IPF lung tissue than in smoker healthy people. Exposure to CSE could upregulate LINC00665/XBP-1 in lung fibroblast-to-myofibroblast transition. Cellular and molecular experiments showed that LINC00665 regulates the expression of XBP-1 by targeting miR-214-3p. LINC00665 expression, was significantly upregulated in BLM-induced mouse lung fibrosis tissues, and LINC00665 knockdown inhibited fibrogenesis in BLM-induced lung fibrosis.
CONCLUSIONS: Our study found that the high expression of LINC00665 is involved in the pathogenesis of smoker IPF and that CSE may positively regulate LINC00665/XBP-1 to participate in lung fibroblast-to-myofibroblast transition. These findings help elucidate the pathogenesis of smoker IPF and may contribute to the development of new targeted drugs for IPF therapy.
摘要：
背景：吸烟可能会影响特发性肺纤维化（IPF）的进展，吸烟强度与IPF呈剂量反应相关。
方法：回顾性分析我院2014年至2018年确诊的IPF患者，并进行随访以确认生存状况和持续时间。并确定吸烟对IPF预后的影响。我们从生物信息学数据库中检索了IPF的信息，以鉴定吸烟者中lncRNAs和蛋白质的差异表达。因此,我们通过细胞实验探索并验证了香烟烟雾暴露(CSE)调节LINC00665/XBP-1参与肺纤维化的机制.我们通过细胞和分子实验阐明了LINC00665和XBP-1之间的机制。并通过使用博来霉素（BLM）诱导的肺纤维化模型验证了沉默LINC00665对肺纤维化的抑制作用。
结果：我们发现，与不吸烟者相比，患有IPF的吸烟者预后较差。LINC00665和XBP-1在IPF肺组织和吸烟者肺组织中的表达均显著上调,此外,LINC00665在吸烟者IPF肺组织中高于吸烟者健康人。暴露于CSE可以上调LINC00665/XBP-1在肺成纤维细胞到肌成纤维细胞的转变。细胞和分子实验表明LINC00665通过靶向miR-214-3p调节XBP-1的表达。LINC00665表达式,在BLM诱导的小鼠肺纤维化组织中显著上调，和LINC00665敲低抑制BLM诱导的肺纤维化中的纤维化。
结论：我们的研究发现LINC00665的高表达与吸烟者IPF的发病机制有关，CSE可能正调控LINC00665/XBP-1参与肺成纤维细胞向肌成纤维细胞的转化。这些发现有助于阐明吸烟者IPF的发病机制，并可能有助于开发新的IPF治疗靶向药物。
方法：回顾性分析我院2014年至2018年确诊的IPF患者，并进行随访以确认生存状况和持续时间。并确定吸烟对IPF预后的影响。我们从生物信息学数据库中检索了IPF的信息，以鉴定吸烟者中lncRNAs和蛋白质的差异表达。因此,我们通过细胞实验探索并验证了香烟烟雾暴露(CSE)调节LINC00665/XBP-1参与肺纤维化的机制.我们通过细胞和分子实验阐明了LINC00665和XBP-1之间的机制。并通过使用博来霉素（BLM）诱导的肺纤维化模型验证了沉默LINC00665对肺纤维化的抑制作用。
结果：我们发现，与不吸烟者相比，患有IPF的吸烟者预后较差。LINC00665和XBP-1在IPF肺组织和吸烟者肺组织中的表达均显著上调,此外,LINC00665在吸烟者IPF肺组织中高于吸烟者健康人。暴露于CSE可以上调LINC00665/XBP-1在肺成纤维细胞到肌成纤维细胞的转变。细胞和分子实验表明LINC00665通过靶向miR-214-3p调节XBP-1的表达。LINC00665表达式,在BLM诱导的小鼠肺纤维化组织中显著上调，和LINC00665敲低抑制BLM诱导的肺纤维化中的纤维化。
结论：我们的研究发现LINC00665的高表达与吸烟者IPF的发病机制有关，CSE可能正调控LINC00665/XBP-1参与肺成纤维细胞向肌成纤维细胞的转化。这些发现有助于阐明吸烟者IPF的发病机制，并可能有助于开发新的IPF治疗靶向药物。
