Abstract
BackgroundAging is a known risk factor of idiopathic pulmonary fibrosis (IPF). However, the pathogenic mechanisms underlying the effects of advanced aging remain largely unknown. Telomeric repeat-containing RNA (TERRA) represents a type of long noncoding RNA. In this study, the regulatory roles of TERRA on human telomeres and mitochondria and IPF epithelial injury model were identified.MethodsBlood samples were collected from patients with IPF (n = 24) and matched control individuals (n = 24). The significance of clinical research on the TERRA expression correlated with pulmonary fibrosis was assessed. The expression levels of TERRA in vivo and in vitro were determined through quantitative real-time polymerase chain reaction analysis. Telomerase activity was observed using a fluorescent quantitative TRAP assay kit. The functions of telomeres, mitochondria, and associated genes were analyzed through RNA interference on TERRA.ResultsTERRA expression levels significantly increased in the peripheral blood mononuclear cells of IPF patients. The expression levels also exhibited a direct and significantly inverse correlation with the percentage of predicted force vital capacity, which is a physiological indicator of fibrogenesis during IPF progression. This finding was confirmed in the epithelial injury model of IPF in vitro. RNA interference on TERRA expression can ameliorate the functions of telomeres; mitochondria; associated genes; components associated with telomeres, such as telomerase reverse transcriptase, telomerase, and cell nuclear antigen, cyclin D1; and mitochondria-associated cyclin E genes, including the MMP and Bcl-2 family. The RNA interference on TERRA expression can also improve the functions of oxidative-stress-associated genes, such as reactive oxygen species, superoxide dismutase, and catalase, and apoptosis-related genes, such as cytochrome c, caspase-9, and caspase-3.ConclusionsIn this study, the regulation of TERRA expression on telomeres and mitochondria during IPF pathogenesis was identified for the first time. The results may provide valuable insights for the discovery of a novel biomarker or therapeutic approach for IPF treatment.
Highlights
Aging is a known risk factor of idiopathic pulmonary fibrosis (IPF)
Clinical research on Telomeric repeat-containing RNA (TERRA) correlation with pulmonary fibrosis We initially assessed the significance of the correlation between clinical research on TERRA expression and pulmonary fibrosis
The percentage of the predicted force vital capacity (FVC%) was significant and was considered a physiological indicator of fibrogenesis during IPF progression [21]. This indicator was used to analyze the correlation of the TERRA expression with pulmonary fibrosis
Summary
Aging is a known risk factor of idiopathic pulmonary fibrosis (IPF). The pathogenic mechanisms underlying the effects of advanced aging remain largely unknown. Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic and progressive fibrosing interstitial pneumonia of unknown cause, and this condition occurs primarily in adults and often develops in the lungs [1]. López-Otín et al proposed several pivotal hallmarks, such as abnormal shortening of telomeres, epigenetic change, and mitochondrial dysfunction, which contribute to the aging process. These hallmarks can occur simultaneously and become interconnected during aging [4]. The mechanistic link among these aging hallmarks in IPF should be investigated
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