American Journal of Respiratory Cell and Molecular Biology

The function of type 2 immunity and mechanisms underlying the initiation of type 2 immunity following sepsis-induced lung injury remain unclear. S1PR2 has been demonstrated to modulate type 2 immunity in the context of asthma and pulmonary fibrosis. Thus, this study aims to investigate the role of type 2 immunity and whether and how S1PR2 regulates type 2 immunity in sepsis. Peripheral type 2 immune response in septic patients and healthy controls were assessed. The impact of S1PR2 on type 2 immunity in septic patients and in a murine model of sepsis was further investigated...

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No abstract text is available yet for this article.

Alveolar type 2 (AT2) and club cells are part of the stem cell niche of the lung and their differentiation is required for pulmonary homeostasis and tissue regeneration. A disturbed crosstalk between fibroblasts and epithelial cells contributes to the loss of lung structure in chronic lung diseases. Therefore, it is important to understand how fibroblasts and lung epithelial cells interact during regeneration. Here we analyzed the interaction of fibroblasts and the alveolar epithelium modelled in air-liquid interface cultures...

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic methods. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2), was elevated in both lungs of patients with pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrotic mice. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix (ECM) deposition of fibroblasts, while overexpression of GOLM1 exerted the opposite effects...

The high mortality of chronic obstructive pulmonary disease (COPD) patients may occur due to pulmonary hypertension (PH). These diseases are highly associated with cigarette smoke (CS) and its key component nicotine use. Here, we created a novel animal model of PH using nicotine (or CS) and hypoxia (N/H) co-exposure. This never-reported model showed a significant early-onset pulmonary vasoremodeling and PH. Using newly-generated complementary smooth muscle (SM)-specific Rieske iron-sulfur protein (RISP) gene knockout (KO) and overexpression (OE) mice, we demonstrate that RISP is critically involved in promoting pulmonary vasoremodeling and PH, which are implemented by oxidative ataxia telangiectasia-mutated (ATM)-mediated DNA damage and NF-κB-dependent inflammation in a reciprocal positive mechanism...

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in COPD patients are poorly understood. In this study, we sought to determine if epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity, and by reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction...

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Respiratory viral infections are frequent causes of acute respiratory distress syndrome (ARDS), a disabling condition with a mortality of up to 46%. The pulmonary endothelium plays an important role in the development of ARDS as well as the pathogenesis of pulmonary fibrosis; however, the therapeutic potential to modulate endothelial-dependent signaling to prevent deleterious consequences has not been well explored. Here we use a clinically relevant influenza A virus infection model, endothelial cell-specific transgenic gain-of-function and loss-of-function mice as well as pharmacologic approaches, and in vitro modeling, to define the mechanism by which S1PR1 expression is dampened during influenza virus infection and determine whether therapeutic augmentation of S1PR1 has the potential to reduce long-term post-viral fibrotic complications...

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Obstructive sleep apnea (OSA), a widespread breathing disorder, leads to intermittent hypoxia (IH). OSA patients and IH-treated rodents exhibit heightened sympathetic nerve activity and hypertension. Previous studies reported transcriptional activation of NADPH oxidases (Nox) by hypoxia-inducible factor-1 (HIF-1) contribute to autonomic dysfunction in IH treated rodents. Lysine acetylation, regulated by lysine acetyltransferase (KATs) and lysine deacetylase (KDACs), activates gene transcription and play an important role in several physiological and pathological processes...

Oxidative stress (OS), inflammation, and endoplasmic reticulum (ER) stress sequentially occur in bronchopulmonary dysplasia (BPD), and all result in DNA damage. When DNA damage becomes irreparable, tumor suppressors increase, followed by apoptosis or senescence. Although cellular senescence contributes to wound healing, its persistence inhibits growth. Therefore, we hypothesized that cellular senescence contributes to BPD progression. Human autopsy lungs were obtained. Sprague-Dawley rat pups exposed to 95% oxygen between postnatal day 1 (P1) to P10 were used as the BPD phenotype...

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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.

It is well known that Fibroblast Growth Factor Receptor 2 (FGFR2) signaling is critical for proper lung development. Recent studies demonstrate that epithelial FGFR2 signaling during the saccular phase of lung development (sacculation) regulates AT1 and AT2 cell differentiation. During sacculation, Platelet-Derived Growth Factor Receptor Alpha-positive (PDGFRA+ ) lung fibroblasts exist as three functional subtypes: contractile myofibroblasts, ECM-producing matrix fibroblasts, and lipofibroblasts. All three subtypes are required during alveolarization to establish a niche that supports alveolar type-2 epithelial (AT2) self-renewal and alveolar type-1 epithelial (AT1) differentiation...

Generation of bioactive truncated oxidized phospholipids (Tr-OxPLs) from oxidation of cell membrane or circulating lipoproteins is a common feature of various pathological states. Scavenger receptor CD36 is involved in lipid transport and acts as a ligand for Tr-OxPLs. Interestingly, both Tr-OxPLs and CD36 are involved in endothelial dysfunction-derived acute lung injury but precise mechanistic connections remain unexplored. In the present study, we investigated the role of CD36 in mediating pulmonary endothelial cell (EC) dysfunction caused by Tr-OxPLs...

Increasing evidence suggests that mitochondrial dysfunction in pulmonary endothelial cells (ECs) plays a causative role in the initiation and progression of pulmonary hypertension (PH); how mitochondria become dysfunctional in PH remains elusive. Mitochondria-derived vesicles (MDVs) are small subcellular vesicles that excise from mitochondria. Whether or not MDVs deregulation causes mitochondrial dysfunction in PH is unknown. This aim of this study was to determine MDVs regulation in ECs and to elucidate how MDVs deregulation in ECs leads to PH...

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