Targeting Airway Smooth Muscle Hypertrophy in Asthma: An Approach Whose Time Has Come

Chetty, Anne; Nielsen, Heber C.

doi:10.2147/jaa.s280247

Cited by 13 publications

(6 citation statements)

References 116 publications

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“…In addition, increased pericyte recruitment to vessels caused by a loss of prolyl hydroxylase domain protein 2 in ECs leads to perivascular fibrosis, right ventricular hypertrophy, and PH independent from any other stimuli [ 140 ]. Hypertrophic airway smooth muscles can limit apoptosis in neighboring myofibroblasts [ 154 ], and such effects may further the vascular remodeling observed in pulmonary vessels.…”

Section: Vascular Pericytes In Pulmonary Fibrosismentioning

confidence: 99%

Role of Sensory Nerves in Pulmonary Fibrosis

Norton

2024

IJMS

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Pulmonary fibrosis results from the deposition and proliferation of extracellular matrix components in the lungs. Despite being an airway disorder, pulmonary fibrosis also has notable effects on the pulmonary vasculature, with the development and severity of pulmonary hypertension tied closely to patient mortality. Furthermore, the anatomical proximity of blood vessels, the alveolar epithelium, lymphatic tissue, and airway spaces highlights the need to identify shared pathogenic mechanisms and pleiotropic signaling across various cell types. Sensory nerves and their transmitters have a variety of effects on the various cell types within the lungs; however, their effects on many cell types and functions during pulmonary fibrosis have not yet been investigated. This review highlights the importance of gaining a new understanding of sensory nerve function in the context of pulmonary fibrosis as a potential tool to limit airway and vascular dysfunction.

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Section: Vascular Pericytes In Pulmonary Fibrosismentioning

confidence: 99%

Role of Sensory Nerves in Pulmonary Fibrosis

Norton

2024

IJMS

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“…Frontiers in Physiology frontiersin.org myofibroblasts by modulating apoptosis (Chetty and Nielsen, 2021).…”

Section: Contribution Of Pericytes To Subepithelial Fibrosis In Aller...mentioning

confidence: 99%

“…Hypertrophy of SMCs increases their contractility and therefore contributes to airway hyperresponsiveness. It has also been suggested that hypertrophic smooth muscle may have a protective effect on neighbouring myofibroblasts by modulating apoptosis ( Chetty and Nielsen, 2021 ). The increased number of SMCs also increases the contraction of airways as well as the responsiveness of the cells to stimuli ( Khan, 2013 ).…”

Section: Allergic Asthma—symptoms Disease Course and Pathological Mec...mentioning

confidence: 99%

Pericytes: The lung-forgotten cell type

Garrison

Bignold

et al. 2023

Front. Physiol.

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Pericytes are a heterogeneous population of mesenchymal cells located on the abluminal surface of microvessels, where they provide structural and biochemical support. Pericytes have been implicated in numerous lung diseases including pulmonary arterial hypertension (PAH) and allergic asthma due to their ability to differentiate into scar-forming myofibroblasts, leading to collagen deposition and matrix remodelling and thus driving tissue fibrosis. Pericyte-extracellular matrix interactions as well as other biochemical cues play crucial roles in these processes. In this review, we give an overview of lung pericytes, the key pro-fibrotic mediators they interact with, and detail recent advances in preclinical studies on how pericytes are disrupted and contribute to lung diseases including PAH, allergic asthma, and chronic obstructive pulmonary disease (COPD). Several recent studies using mouse models of PAH have demonstrated that pericytes contribute to these pathological events; efforts are currently underway to mitigate pericyte dysfunction in PAH by targeting the TGF-β, CXCR7, and CXCR4 signalling pathways. In allergic asthma, the dissociation of pericytes from the endothelium of blood vessels and their migration towards inflamed areas of the airway contribute to the characteristic airway remodelling observed in allergic asthma. Although several factors have been suggested to influence this migration such as TGF-β, IL-4, IL-13, and periostin, recent evidence points to the CXCL12/CXCR4 pathway as a potential therapeutic target. Pericytes might also play an essential role in lung dysfunction in response to ageing, as they are responsive to environmental risk factors such as cigarette smoke and air pollutants, which are the main drivers of COPD. However, there is currently no direct evidence delineating the contribution of pericytes to COPD pathology. Although there is a lack of human clinical data, the recent available evidence derived from in vitro and animal-based models shows that pericytes play important roles in the initiation and maintenance of chronic lung diseases and are amenable to pharmacological interventions. Therefore, further studies in this field are required to elucidate if targeting pericytes can treat lung diseases.

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“…Fortunately, understanding the mechanisms by which sex steroids influence structural cells of the airways has garnered new interest with novel findings from researchers working on ASM, epithelial cells and fibroblast in the lungs [ 5 , 39 , 201 , 207 , 208 ]. Sex steroids influence structural cells of the airways and immune cells independently.…”

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

Borkar

Combs

Sathish

2022

Cells

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A multitude of evidence has suggested the differential incidence, prevalence and severity of asthma between males and females. A compilation of recent literature recognized sex differences as a significant non-modifiable risk factor in asthma pathogenesis. Understanding the cellular and mechanistic basis of sex differences remains complex and the pivotal point of this ever elusive quest, which remains to be clarified in the current scenario. Sex steroids are an integral part of human development and evolution while also playing a critical role in the conditioning of the immune system and thereby influencing the function of peripheral organs. Classical perspectives suggest a pre-defined effect of sex steroids, generalizing estrogens popularly under the “estrogen paradox” due to conflicting reports associating estrogen with a pro- and anti-inflammatory role. On the other hand, androgens are classified as “anti-inflammatory,” serving a protective role in mitigating inflammation. Although considered mainstream and simplistic, this observation remains valid for numerous reasons, as elaborated in the current review. Women appear immune-favored with stronger and more responsive immune elements than men. However, the remarkable female predominance of diverse autoimmune and allergic diseases contradicts this observation suggesting that hormonal differences between the sexes might modulate the normal and dysfunctional regulation of the immune system. This review illustrates the potential relationship between key elements of the immune cell system and their interplay with sex steroids, relevant to structural cells in the pathophysiology of asthma and many other lung diseases. Here, we discuss established and emerging paradigms in the clarification of observed sex differences in asthma in the context of the immune system, which will deepen our understanding of asthma etiopathology.

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Targeting Airway Smooth Muscle Hypertrophy in Asthma: An Approach Whose Time Has Come

Cited by 13 publications

References 116 publications

Role of Sensory Nerves in Pulmonary Fibrosis

Role of Sensory Nerves in Pulmonary Fibrosis

Pericytes: The lung-forgotten cell type

Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

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