American Journal of Respiratory Cell and Molecular Biology

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The cystic fibrosis transmembrane conductance regulator (CFTR) is a tightly regulated anion channel that mediates chloride and bicarbonate conductance in many epithelia and in other tissues, but whether its regulation varies depending on the cell type has not been investigated. Epithelial CFTR expression is highest in rare cells called ionocytes. We studied CFTR regulation in control and ionocyte-enriched cultures by transducing bronchial basal cells with adenoviruses that contain only eGFP or FOXI1 + eGFP as separate polypeptides...

Hypoxia-inducible factor (HIF) has received much attention as a potential pulmonary hypertension (PH) treatment target because inhibition of HIF reduces the severity of established PH in rodent models. However, the limitations of small animal models of PH in predicting the therapeutic effects of pharmacologic interventions in human PH are well known. Therefore, we sought to interrogate the role of HIFs in driving the activated phenotype of PH cells from human and bovine vessels. We first established that pulmonary arteries (PAs) from human and bovine PH lungs exhibit markedly increased expression of direct HIF target genes (CA9, GLUT1, and NDRG1), as well as of cytokines/chemokines (CCL2, CSF2, CXCL12, and IL6), growth factors (FGF1, FGF2, PDGFb, and TGFA), and apoptosis resistance genes (BCL2, BCL2L1, and BIRC5)...

Various environmental compounds are inducers of lung injury. Mitochondria are crucial organelles that can be impacted by many lung diseases. NecroX is an indole-derived antioxidant that specifically targets mitochondria. We aimed to evaluate therapeutic potential and related molecular mechanisms of NecroX in preclinical models of fatal lung injury. We investigated the therapeutic effects of NecroX on two different experimental models of lung injury induced by polyhexamethylene guanidine (PHMG) and bleomycin, respectively...

Progressive pulmonary fibrosis results from a dysfunctional tissue repair response and is characterized by fibroblast proliferation, activation, invasion, and extracellular matrix accumulation. Lung fibroblast heterogeneity is well recognized. With single cell RNA-sequencing (scRNA-seq), fibroblast subtypes have been reported by recent studies. However, the roles of fibroblast subtypes in effector functions in lung fibrosis are not well understood. In this study, we incorporated the recently published scRNA-seq datasets on murine lung samples of fibrosis models and human lung samples of fibrotic diseases and analyzed fibroblast gene signatures...

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Reduced expression and/or activity of Kv1.5 channels (encoded by KCNA5 ) is a common hallmark in human or experimental pulmonary arterial hypertension (PAH). Likewise, genetic variants in KCNA5 have been found in PAH patients, but their functional consequences and potential impact on the disease are largely unknown. Herein, we aimed to characterize the functional consequences of 7 KCNA5 variants found in a cohort of PAH patients. Potassium currents were recorded by patch-clamp technique in HEK293 cells transfected with WT or mutant Kv1...

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Clinical observations suggest that the source of primary infection accounts for a major determinant of further nosocomial pneumonia in critically ill sepsis patients. We herein addressed the impact of primary non-pulmonary or pulmonary septic insults on lung immunity using relevant double-hit animal models. C57BL/6J mice were first subjected to either polymicrobial peritonitis induced by caecal ligation and puncture (CLP) or bacterial pneumonia induced by intratracheal challenge with Escherichia coli. Seven days after, post-septic mice received intratracheal challenge with Pseudomonas aeruginosa...

Epithelial-mesenchymal transition (EMT) contributes to airway remodeling, a predominant feature of asthma. Dedicator of cytokinesis 2 (DOCK2) is an innate immune signaling molecule involved in vascular remodeling. However, it is unknown if DOCK2 plays a role in airway remodeling during asthma development. In this study, we found that DOCK2 is highly induced in both normal human bronchial epithelial cells (NHBECs) treated with house dust mite (HDM) extract and human asthmatic airway epithelium. DOCK2 is also upregulated by transforming growth factor β1 (TGF-β1) during EMT of HBECs...

In idiopathic pulmonary fibrosis (IPF), the normal delicate lung architecture is replaced with rigid extracellular matrix (ECM) due to accumulation of activated myofibroblasts and excessive deposition of ECM. Lamins have a role in fostering mechanosignaling from the ECM to the nucleus. Although there is a growing number of studies on lamins and associated diseases, there are no prior reports linking aberrations in lamins with pulmonary fibrosis. Here, we discovered through analysis of our RNA-seq data, a novel isoform of lamin A/C that is more highly expressed in IPF compared to control lung...

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of SARS-CoV-2 infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in COVID-19 pneumonia patients capable of predicting post-COVID pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to hospital with bilateral COVID-19 pneumonia. We classified patients in two groups according to severity, and blood samples to measure MMP1, MMP7, periostin and VEGF, respiratory function tests and HRCT imaging were obtained at 2 and 12 months after hospital discharge...

Idiopathic pulmonary fibrosis (IPF) is a progressive aging-related lung disease that is associated with increased lung cancer risk. Although previous studies have shown that IPF worsens the survival of lung cancer patients, whether IPF independently affects cancer malignancy and prognosis remains inconclusive. Extracellular vesicles (EVs) have recently emerged as active carriers of molecular biomarkers and mediators of intercellular communication in lung homeostasis and pathogenesis. EV cargo-mediated fibroblast-tumor cell communication might participate in the development and progression of lung cancer by modulating various signaling pathways...

The lung epithelium is dynamic, capable of considerable structural and functional plasticity in response to pathogen challenges. Our lab has demonstrated that an inhaled combination of a Toll-like receptor (TLR)2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust, protection against otherwise lethal Pseudomonas aeruginosa pneumonias. We have previously shown that intact epithelial TLR signaling and generation of multisource epithelial reactive oxygen species (ROS) are both required for the inducible protection...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.