Role of Lung Apolipoprotein A-I in Idiopathic Pulmonary Fibrosis

Kim, Tae Hoon; Lee, Yoo Hoon; Kim, Kyung Hun; Lee, Shin Hwa; Yeon, Ji; Shin, Eun Ju; Jung, Seok Won; Jang, An Soo; Park, Sung Woo; Uh, Soo Taek; Kim, Young Hoon; Park, Jai Soung; Sin, Hwa Gyoun; Youm, Wook; Koh, Eun Suk; Cho, Sun Young; Paik, Young Ki; Rhim, Taiyoun; Park, Choon-Sik

doi:10.1164/rccm.200905-0659oc

Cited by 98 publications

(45 citation statements)

References 55 publications

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“…The functional role of APOA2, the most downregulated differentially expressed proteins identified in the present study, has not been reported in IPF in the past. However, low concentrations APOA1 were found in bronchoalveolar lavage fluids from subjects with IPF [48]. This suggested the involvement of APOA2 in the pathophysiology of IPF.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-Based Proteomics Reveals Novel Biomarkers for Idiopathic Pulmonary Fibrosis

et al. 2017

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Idiopathic pulmonary fibrosis (IPF) is a gradual lung disease with a survival of less than 5 years post-diagnosis for most patients. Poor molecular description of IPF has led to unsatisfactory interpretation of the pathogenesis of this disease, resulting in the lack of successful treatments. The objective of this study was to discover novel noninvasive biomarkers for the diagnosis of IPF. We employed a coupled isobaric tag for relative and absolute quantitation (iTRAQ)-liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach to examine protein expression in patients with IPF. A total of 97 differentially expressed proteins (38 upregulated proteins and 59 downregulated proteins) were identified in the serum of IPF patients. Using String software, a regulatory network containing 87 nodes and 244 edges was built, and the functional enrichment showed that differentially expressed proteins were predominantly involved in protein activation cascade, regulation of response to wounding and extracellular components. A set of three most significantly upregulated proteins (HBB, CRP and SERPINA1) and four most significantly downregulated proteins (APOA2, AHSG, KNG1 and AMBP) were selected for validation in an independent cohort of IPF and other lung diseases using ELISA test. The results confirmed the iTRAQ profiling results and AHSG, AMBP, CRP and KNG1 were found as specific IPF biomarkers. ROC analysis indicated the diagnosis potential of the validated biomarkers. The findings of this study will contribute in understanding the pathogenesis of IPF and facilitate the development of therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

iTRAQ-Based Proteomics Reveals Novel Biomarkers for Idiopathic Pulmonary Fibrosis

et al. 2017

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“…BAL had been performed in the most affected lobe by computed tomography in the 24 subjects without any immunosuppressive therapy and in the right middle lobe of 14 normal controls, as described previously[17]. The supernatant was separated from cell pellets by centrifugation at 500 × g for 5 minutes.…”

Section: Methodsmentioning

confidence: 99%

A promoter SNP rs4073T>A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode

et al. 2011

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BackgroundInterleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF.MethodsOne promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay.ResultsThe minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002).ConclusionThe common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

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“…There is emerging evidence that Apo A-I has a critical role in protecting pulmonary artery and airway function as well as preventing inflammation and collagen deposition in the lung (33). Local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis (34). Intermittent hypoxic exercise has been shown to stimulate the levels of Apo A-I and strengthen the metabolism of lipids, and may have certain functions in cardiovascular disease treatment (35).…”

Section: Discussionmentioning

confidence: 99%

Differential plasma proteome analysis in patients with high-altitude pulmonary edema at the acute and recovery phases

Yang

Guan

et al. 2014

Experimental and Therapeutic Medicine

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This study aimed to investigate the differential expression of plasma proteins in patients suffering from high-altitude pulmonary edema (HAPE) at different phases. A complete proteomic analysis was performed using two-dimensional gel electrophoresis followed by mass spectrometry in three patients with HAPE at the acute stage and recovery phase. Comparisons between the expression patterns of the patients with HAPE at the two different phases led to the identification of eight protein spots with a >1.5-fold difference in expression between the acute and recovery phases. These differentially expressed proteins were apolipoproteins, serum amyloid P component, complement components and others. Apolipoprotein A-I (Apo A-I), serum amyloid P component and fibrinogen were overexpressed in the patients with HAPE in the acute stage compared with their expression levels in the recovery phase. However, Apo A-IV and antithrombin-III were overexpressed in the patients with HAPE in the recovery phase compared with their expression levels in the acute stage. The results indicate that the differential plasma proteome in patients with HAPE may be associated with the occurrence of HAPE, and the expression changes of Apo A-I and A-IV may offer further understanding of HAPE to aid its prognosis, diagnosis and treatment.

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Role of Lung Apolipoprotein A-I in Idiopathic Pulmonary Fibrosis

Abstract: Alterations of several inflammatory and antiinflammatory proteins in the lungs may be related to the pathogenesis of IPF, and local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis.

Cited by 98 publications

References 55 publications

iTRAQ-Based Proteomics Reveals Novel Biomarkers for Idiopathic Pulmonary Fibrosis

iTRAQ-Based Proteomics Reveals Novel Biomarkers for Idiopathic Pulmonary Fibrosis

A promoter SNP rs4073T>A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode

Differential plasma proteome analysis in patients with high-altitude pulmonary edema at the acute and recovery phases

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