Altered expression pattern of immune response-related genes and isoforms in hypersensitivity pneumonitis lung fibroblasts.

Hypersensitivity pneumonitis (HP) is an immune-mediated inflammatory interstitial lung disease that may evolve to pulmonary fibrosis, a progressive disorder with a poor prognosis characterized by fibroblast activation and extracellular matrix accumulation. In HP lung fibroblasts, the gene expression of proteins involved in the interaction with the immune response, their isoforms, and how they influence their phenotype have yet to be elucidated. We analyzed the expression and splicing variants of 16 target genes involved in the interaction between HP fibroblasts and immune signaling and evaluated possible correlations with clinical data.

Determination of loss of chromosome Y in peripheral blood cells in males with idiopathic pulmonary fibrosis.

https://bit.ly/3ZIQHKi

Mir-155-5p targets TP53INP1 to promote proliferative phenotype in hypersensitivity pneumonitis lung fibroblasts.

Background: Hypersensitivity pneumonitis (HP) is an inflammatory disorder affecting lung parenchyma and often evolves into fibrosis (fHP). The altered regulation of genes involved in the pathogenesis of the disease is not well comprehended, while the role of microRNAs in lung fibroblasts remains unexplored.

Methods: We used integrated bulk RNA-Seq and enrichment pathway bioinformatic analyses to identify differentially expressed (DE)-miRNAs and genes (DEGs) associated with HP lungs.

HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.

High mobility group A1 (HMGA1) chromatin regulators are upregulated in diverse tumors where they portend adverse outcomes, although how they function in cancer remains unclear. Pancreatic ductal adenocarcinomas (PDACs) are highly lethal tumors characterized by dense desmoplastic stroma composed predominantly of cancer-associated fibroblasts and fibrotic tissue. Here, we uncover an epigenetic program whereby HMGA1 upregulates FGF19 during tumor progression and stroma formation.

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts.

Wood Smoke Extract Promotes Extracellular Matrix Remodeling in Normal Human Lung Fibroblasts.

Wood smoke (WS) contains many harmful compounds, including polycyclic aromatic hydrocarbons (PAHs). WS induces inflammation in the airways and lungs and can lead to the development of various acute and chronic respiratory diseases. Pulmonary fibroblasts are the main cells involved in the remodeling of the extracellular matrix (ECM) during the WS-induced inflammatory response.

Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity.

Tuberculosis (TB), caused by (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB.

Risk factors associated with the development of interstitial lung abnormalities.

Background: Around 8-10% of individuals over 50 years of age present interstitial lung abnormalities (ILAs), but their risk factors are uncertain.

Methods: From 817 individuals recruited in our lung ageing programme at the Mexican National Institute of Respiratory Diseases, 80 (9.7%) showed ILAs and were compared with 564 individuals of the same cohort with normal high-resolution computed tomography to evaluate demographic and functional differences, and with 80 individuals randomly selected from the same cohort for biomarkers.

Antitumor Therapy under Hypoxic Microenvironment by the Combination of 2-Methoxyestradiol and Sodium Dichloroacetate on Human Non-Small-Cell Lung Cancer.

A hypoxic microenvironment is a hallmark in different types of tumors; this phenomenon participates in a metabolic alteration that confers resistance to treatments. Because of this, it was proposed that a combination of 2-methoxyestradiol (2-ME) and sodium dichloroacetate (DCA) could reduce this alteration, preventing proliferation through the reactivation of aerobic metabolism in lung adenocarcinoma cell line (A549). A549 cells were cultured in a hypoxic chamber at 1% O for 72 hours to determine the effect of this combination on growth, migration, and expression of hypoxia-inducible factors (HIFs) by immunofluorescence.

CX3CL1 and CX3CR1 could be a relevant molecular axis in the pathophysiology of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic and progressive disease of unknown cause. It is characterized by the aberrant activation of the bronchioalveolar epithelium, the formation of fibroblast foci and the excessive production extracellular matrix. The cellular and molecular mechanisms that contribute to the pathobiology of the disease are unclear.

Risk factors associated with the detection of pulmonary emphysema in older asymptomatic respiratory subjects.

Background: Several lung structural and functional abnormalities may occur associated with aging, including emphysema. In this study, we evaluated the frequency and risk factors associated with emphysema in respiratory asymptomatic individuals enrolled in our Lung Aging Program. From a cohort of 687 subjects, we found by high-resolution computed tomography (HRCT) 29 individuals (4%) with emphysematous changes that were compared with 87 controls (3:1) randomly selected from the same cohort.

Impaired autophagic activity and ATG4B deficiency are associated with increased endoplasmic reticulum stress-induced lung injury.

Aging is the main risk factor for the development of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal lung disorder. Although the pathogenic mechanisms are uncertain, endoplasmic reticulum (ER) stress and impaired proteostasis that have been linked with aging are strongly associated with the pathogenesis of IPF. Using the Atg4b-deficient mice as a model, that partially reproduces the autophagy deficient conditions reported in aging and IPF lungs, we show for the first time how autophagy impairment and ER stress induction, contribute simultaneously to development of lung fibrosis in vivo.

Upregulation and Nuclear Location of MMP28 in Alveolar Epithelium of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive aging-associated disease of unknown etiology. A growing body of evidence indicates that aberrant activated alveolar epithelial cells induce the expansion and activation of the fibroblast population, leading to the destruction of the lung architecture. Some matrix metalloproteinases (MMPs) are upregulated in IPF, indicating that they may be important in the pathogenesis and/or progression of IPF.

Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined.

FEV1 inversely correlates with metalloproteinases 1, 7, 9 and CRP in COPD by biomass smoke exposure.

Background: Matrix metalloproteinases (MMPs) and C-reactive protein (CRP) are involved in chronic obstructive pulmonary disease (COPD) pathogenesis. The aim of the present work was to determine plasma concentrations of MMPs and CRP in COPD associated to biomass combustion exposure (BE) and tobacco smoking (TS).

Methods: Pulmonary function tests, plasma levels of MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP were measured in COPD associated to BE (n = 40) and TS (n =40) patients, and healthy non-smoking (NS) healthy women (controls, n = 40).

Matrix metalloproteinase (MMP)-1 induces lung alveolar epithelial cell migration and proliferation, protects from apoptosis, and represses mitochondrial oxygen consumption.

Idiopathic pulmonary fibrosis is a devastating lung disorder of unknown etiology. Although its pathogenesis is unclear, considerable evidence supports an important role of aberrantly activated alveolar epithelial cells (AECs), which produce a large variety of mediators, including several matrix metalloproteases (MMPs), which participate in fibroblast activation and lung remodeling. MMP-1 has been shown to be highly expressed in AECs from idiopathic pulmonary fibrosis lungs although its role is unknown.

Hypermethylation-mediated silencing of p14(ARF) in fibroblasts from idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. A conspicuous feature is the formation and persistence of fibroblastic/myofibroblastic foci throughout the lung parenchyma. Mechanisms remain unknown, but data indicate that fibroblasts acquire an antiapoptotic phenotype.

Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung.

Methods And Findings: Using oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF lungs and was also significantly elevated in bronchoalveolar lavage from IPF patients.