American Journal of Respiratory Cell and Molecular Biology

Pulmonary hypertension (PH) is a life-threatening syndrome associated with hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which exhibit similar features to cancer cells. Currently, there is no curative treatment for PH. LKB1 is known as a tumor suppressor gene with an anti-proliferative effect on cancer cells. However, its role and mechanism in the development of PH remain unclear. Gain-and loss-of-function strategies were used to elucidate the mechanisms of LKB1 in regulating the occurrence and progression of PH...

Nicotine exposure in the context of smoking or vaping worsens airway function. Although commonly thought to exert effects through the peripheral nervous system, we previously showed airway smooth muscle (ASM) expresses nicotinic acetylcholine receptors (nAChRs), particularly alpha7 subtype (α7nAChR) with functional effects on contractility and metabolism. However, the mechanisms of nAChR regulation and downstream effects in ASM are not fully understood. Using human ASM cells from non-asthmatics vs. mild-moderate asthmatics, we tested the hypothesis that nAChR-specific ER chaperones RIC-3 and TMEM35 promote cell surface localization of α7nAChR with downstream influence on its functionality: effects exacerbated by inflammation...

The role of circRNAs in sepsis-induced lung injury is not clear. This study investigated the role and molecular mechanism of a novel circRNA in sepsis-induced lung injury and explored its prognostic value in sepsis patients. In this study, aberrant circRNA expression profiling in lung tissues from mice with sepsis-induced lung injury was analyzed using high-throughput sequencing. CircRNA-Cacna1d was verified by quantitative real-time polymerase chain reaction, and its biological function in sepsis-induced lung injury was validated in vitro and in vivo ...

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No abstract text is available yet for this article.

Organoid 3D systems are powerful platforms to study development and disease. Recently, the complexity of lung organoid models derived from adult mouse and human stem cells has increased substantially in terms of cellular composition and structural complexity. However, a murine lung organoid system with a clear integrated endothelial compartment is still missing. Here, we describe a novel method that adds another level of intricacy to our published bronchioalveolar lung organoid (BALO) model by microinjection of FACS-sorted lung endothelial cells (ECs) into differentiated organoid cultures...

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. Endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the arterial-to-capillary-to-vein axis...

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Right ventricular (RV) fibrosis is associated with RV dysfunction in a variety of RV pressure-loading conditions where RV mechanical stress is increased, but the underlying mechanisms driving RV fibrosis are incompletely understood. In pulmonary and cardiovascular diseases characterized by elevated mechanical stress and transforming growth factor - beta-1 (TGF-β1) signaling, myocardin-related transcription factor A (MRTF-A) is a mechanosensitive protein critical to driving myofibroblast transition and fibrosis...

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A-kinase-anchoring proteins (AKAPs) act as scaffold proteins that anchor the regulatory subunits of the cAMP-dependent protein kinase A (PKA) to coordinate and compartmentalize signaling elements and signals downstream of Gs-coupled G protein-coupled receptors (GPCRs). The beta-2-adrenoceptor (β2 AR), as well as the Gs-coupled EP2 and EP4 receptor subtypes of the E-prostanoid (EP) receptor subfamily, are effective regulators of multiple airway smooth muscle (ASM) cell functions whose dysregulation contributes of asthma pathobiology...

C-X-C motif chemokine ligand 14 (CXCL14) is expressed in the airway epithelial cells of patients with asthma. However, the mechanisms of CXCL14 secretion and its effects on asthma pathogenesis remain unclear. Here, we investigated the role of CXCL14 in allergic airway inflammation and its effects on eosinophil infiltration. Our findings showed that Alternaria alternata , a major environmental allergen, stimulated CXCL14 secretion from airway epithelial cells via reactive oxygen species (ROS) generated in mitochondrial oxidative phosphorylation (OXPHOS) complexes, especially in OXPHOS complex II...

Expanding upon the critical advancements brought forth by single-cell omics in pulmonary hypertension (PH) research, this review delves deep into how these technologies have been piloted in a new era of understanding this complex disease. By leveraging the power of single cell transcriptomics (scRNA-seq), researchers can now dissect the complicated cellular ecosystem of the lungs, examining the key players such as endothelial cells, smooth muscle cells, pericytes, and immune cells, and their unique roles in the pathogenesis of PH...

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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.

Severe lung injury requiring mechanical ventilation may lead to secondary fibrosis. Senescence, a cell response characterized by cell cycle arrest and a shift towards a proinflammatory/profibrotic phenotype, is one of the involved mechanisms. Here, we explore the contribution of mechanical stretch as trigger of senescence of the respiratory epithelium and its link with fibrosis. Human lung epithelial cells and fibroblasts were exposed in vitro to mechanical stretch, and senescence assessed. In addition, fibroblasts were exposed to culture media preconditioned by senescent epithelial cells and their activation was studied...