Idiopathic Pulmonary Fibrosis

Cai

BioMed Research International

et al. 2021

Objective. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, high-mortality lung disease, but its pathogenesis is still unclear. Our purpose was to explore potential genes and molecular mechanisms underlying IPF. Methods. IPF-related data were obtained from the GSE99621 dataset. Differentially expressed genes (DEGs) were identified between IPF and controls. Their biological functions were analyzed. The relationships between DEGs and microRNAs (miRNAs) were predicted. DEGs and pathways were validated in a microarray dataset. A protein-protein interaction (PPI) network was constructed based on these common DEGs. Western blot was used to validate hub genes in IPF cell models by western blot. Results. DEGs were identified for IPF than controls in the RNA-seq dataset. Functional enrichment analysis showed that these DEGs were mainly enriched in immune and inflammatory response, chemokine-mediated signaling pathway, cell adhesion, and other biological processes. In the miRNA-target network based on RNA-seq dataset, we found several miRNA targets among all DEGs, like RAB11FIP1, TGFBR3, and SPP1. We identified 304 upregulated genes and 282 downregulated genes in IPF compared to controls both in the microarray and RNA-seq datasets. These common DEGs were mainly involved in cell adhesion, extracellular matrix organization, oxidation-reduction process, and lung vasculature development. In the PPI network, 3 upregulated and 4 downregulated genes could be considered hub genes, which were confirmed in the IPF cell models. Conclusion. Our study identified several IPF-related DEGs that could become potential biomarkers for IPF. Large-scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Section: Discussionmentioning

confidence: 99%

[Retracted] Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis

Cai

BioMed Research International

et al. 2021

“…Raghu's case-control study also found that serum HE4 was significantly elevated in patients with idiopathic pulmonary fibrosis (CF) [7]. In this experiment, the level of HE4 increased significantly when hyperoxia induced alveolar epithelial cell injury in rats.…”

Section: Discussionmentioning

confidence: 51%

“…HE4 is a secreted glycoprotein that belongs to the WFDC domain family, a member of the antiprotease family consisting of the whey acidic protein (WAP) domain [3], and high expression of HE4 mRNA can be detected in the trachea and lung [4]. Knockout of this gene in animal studies can cause alveolar vascular dysplasia and severe dyspnea [5,6]; and in pulmonary fibrosis diseases, HE4 interferes with pulmonary fibrosis by regulating matrix metalloproteinases (MMPs) signaling pathway and the remodeling process of the alveolar extracellular matrix [3,[7][8][9]. The key link in the pathophysiological process of BPD is acute lung injury and abnormal remodeling of the matrix after injury.…”

Section: Introductionmentioning

confidence: 99%

Study on the mechanism of HE4 in hyperoxia-induced alveolar damage in rats

Yan

Feng

Gao

et al. 2022

Preprint

Objective: This study investigated the mechanism of human epididymis protein 4 (HE4) in hyperoxia-induced alveolar damage in rats. Methods: The pathological changes of SD rat lung tissue were detected by hematoxylin-eosin staining. Plasma protein levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of mRNA was detected by real-time RT-PCR. Results: Hyperoxia intervention within 7 days could induce acute lung injury in neonatal SD rats. Hyperoxia induction can increase HE4, MMP9 and TIMP1 in plasma and tissue of neonatal SD rats. By overexpressing and silencing HE4 gene in neonatal rat primary alveolar type II epithelial cells, we found that HE4 protein activates the phosphorylation of ERK and p65, activates the downstream MMP9 signaling pathway, inhibits MMP9 mRNA expression, inhibits protein activity, and reduces COLI degradation, increases collagen secretion, promoting matrix remodeling and fibrosis. Conclusion: HE4 mediates the pathophysiological process of hyperoxia-induced lung injury in rats through ERK, MMP9 and TIMP1 signaling pathways. HE4 overexpression mediates lung basal remodeling and lung injury.

“…11,12 However, they are neither able to predict disease progression nor are they routinely available in clinical practice. 13 Recently, Maher and colleagues have conducted a large prospective study of patients with IPF to investigate the predictive power of selected biomarkers and to identify individuals with IPF at risk of progression or death. Among all biomarkers examined, including cytokines, chemokines, growth factors, extracellular matrix proteins and markers of epithelial injury, the authors found that serum levels of Carbohydrate Antigen 19-9 (CA 19-9), a marker of epithelial damage, was significantly associated to disease progression in the first year of follow-up.…”

Section: Introductionmentioning

confidence: 99%

CA 19-9 serum levels in patients with end-stage idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs): Correlation with functional decline

et al. 2020

Idiopathic pulmonary fibrosis presents a progressive and heterogeneous functional decline. CA 19-9 has been proposed as biomarker to predict disease course, but its role remains unclear. We assessed CA 19-9 levels and clinical data in end-stage ILD patients (48 IPF and 20 non-IPF ILD) evaluated for lung transplant, to correlate these levels with functional decline. Patients were categorized based on their rate of functional decline as slow (n = 20; ΔFVC%pred ≤ 10%/year) or rapid progressors (n = 28; ΔFVC%pred ≥ 10%/year). Nearly half of the entire patients (n = 32; 47%) had CA 19-9 levels ≥37kU/L. CA 19-9 levels in IPF were not different from non-IPF ILD populations, however, the latter group had a median CA 19-9 level above the normal cut-off value of 37 KU/l (60 [17–247] kU/L). Among IPF patients, CA 19-9 was higher in slow than in rapid progressors with a trend toward significance (33vs17kU/L; p = 0.055). In the whole population, CA19-9 levels were inversely related with ΔFVC/year (r = −0.261; p = 0.03), this correlation remained in IPF patients, particularly in rapid progressors (r = −0.51; p = 0.005), but not in non. Moreover, IPF rapid progressors with normal CA 19-9 levels showed the greater ΔFVC/year compared to those with abnormal CA 19-9 (0.95 vs. 0.65 L/year; p = 0.03). In patients with end-stage ILD, CA 19-9 may represent a marker of disease severity, whereas its level is inversely correlated with functional decline, particularly among IPF rapid progressors.