Publications by authors named "Zoe Mark"
Background And Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling.
View Article and Find Full Text PDFObesity is a risk factor for severe influenza, and asthma exacerbations caused by respiratory viral infections. We investigated mechanisms that increase the severity of airway disease related to influenza in obesity using cells derived from obese and lean individuals, and and models. Primary human nasal epithelial cells (pHNECs) derived from obese compared with lean individuals developed increased inflammation and injury in response to influenza A virus (IAV).
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- * Miro1, a protein that aids in mitochondrial movement, is linked to the organization of mitochondria in lung cells; its deletion causes mitochondria to cluster around the nucleus.
- * In a study using a mouse model, researchers found that deleting Miro1 in specific lung cells increases inflammation and hinders the resolution of allergic responses, highlighting the role of mitochondrial dynamics in allergic asthma.
Mitoquinone mesylate attenuates pathological features of lean and obese allergic asthma in mice.
Am J Physiol Lung Cell Mol Physiol
February 2023
Obesity is associated with severe, difficult-to-control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. Using a mouse model of house dust mite (HDM)-induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness (AHR).
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- - Influenza neuraminidase (NA) is crucial for the virus to exit infected cells, and its function relies on disulfide bonds, which may be facilitated by protein disulfide isomerase (PDI)A3.
- - Researchers investigated the role of PDIA3 in the maturation and activity of NA using various assays, discovering that the interaction between NA and PDIA3 is essential for NA activity and overall viral propagation.
- - The use of a PDI-specific inhibitor (LOC14) in mouse models showed reduced NA activity and viral burden, suggesting that targeting PDIA3 could be a new strategy for developing antiviral treatments against influenza.
Mitochondria regulate a myriad of cellular functions. Dysregulation of mitochondrial control within airway epithelial cells has been implicated in the pro-inflammatory response to allergens in asthma patients. Because of their multifaceted nature, mitochondrial structure must be tightly regulated through fission and fusion.
View Article and Find Full Text PDFBackground: The role of club cells in the pathology of idiopathic pulmonary fibrosis (IPF) is not well understood. Protein disulfide isomerase A3 (PDIA3), an endoplasmic reticulum-based redox chaperone required for the functions of various fibrosis-related proteins; however, the mechanisms of action of PDIA3 in pulmonary fibrosis are not fully elucidated.
Objectives: To examine the role of club cells and PDIA3 in the pathology of pulmonary fibrosis and the therapeutic potential of inhibition of PDIA3 in lung fibrosis.