Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells

Stasiak, S.E.; Jamieson, R.; Bouffard, Jeff; Cram, Erin J.; Parameswaran, Harikrishnan

doi:10.1126/sciadv.aba1149

Cited by 14 publications

(9 citation statements)

References 41 publications

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“…These regulatory mechanisms (or aberrations thereof) are likely to play an important role in airway remodelling. On shorter timescales Stasiak et al (2020) show that ECM regulates agonistinduced calcium oscillations in ASM cells; calcium responses in healthy donor ASM cells and stiffened underlying ECM were consistent with responses that would be expected with significantly higher agonist dose. Similarly, interactions between the ASM and a stiffer ECM environment have been shown to lead to increased ASM contractility (Polio et al, 2019) and enough to lead to hyperresponsiveness (Jamieson et al, 2021).…”

Section: Discussionsupporting

confidence: 64%

The role of mathematical models in designing mechanopharmacological therapies for asthma

Irons

Brook

2022

Front. Syst. Biol.

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Healthy lung function depends on a complex system of interactions which regulate the mechanical and biochemical environment of individual cells to the whole organ. Perturbations from these regulated processes give rise to significant lung dysfunction such as chronic inflammation, airway hyperresponsiveness and airway remodelling characteristic of asthma. Importantly, there is ongoing mechanobiological feedback where mechanical factors including airway stiffness and oscillatory loading have considerable influence over cell behavior. The recently proposed area of mechanopharmacology recognises these interactions and aims to highlight the need to consider mechanobiology when identifying and assessing pharmacological targets. However, these multiscale interactions can be difficult to study experimentally due to the need for measurements across a wide range of spatial and temporal scales. On the other hand, integrative multiscale mathematical models have begun to show success in simulating the interactions between different mechanobiological mechanisms or cell/tissue-types across multiple scales. When appropriately informed by experimental data, these models have the potential to serve as extremely useful predictive tools, where physical mechanisms and emergent behaviours can be probed or hypothesised and, more importantly, exploited to propose new mechanopharmacological therapies for asthma and other respiratory diseases. In this review, we first demonstrate via an exemplar, how a multiscale mathematical model of acute bronchoconstriction in an airway could be exploited to propose new mechanopharmacological therapies. We then review current mathematical modelling approaches in respiratory disease and highlight hypotheses generated by such models that could have significant implications for therapies in asthma, but that have not yet been the subject of experimental attention or investigation. Finally we highlight modelling approaches that have shown promise in other biological systems that could be brought to bear in developing mathematical models for optimisation of mechanopharmacological therapies in asthma, with discussion of how they could complement and accelerate current experimental approaches.

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Section: Discussionsupporting

confidence: 64%

The role of mathematical models in designing mechanopharmacological therapies for asthma

Irons

Brook

2022

Front. Syst. Biol.

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“…Smooth muscle cells (SMC) are a critical contractile component of the airway and an essential contributor to the local production of inflammatory and growth factor products to repair and renew the lung ( 59 – 61 ). To evaluate the SMC distribution and numbers, we performed staining for the nucleus (DAPI, blue staining), SARS-CoV-2 protein M (green staining), smooth muscle actin (SMA, a small muscle marker, red staining), and SARS-CoV-2-mRNA (S-sense for the replicating virus) ( Figure 8 ).…”

Section: Resultsmentioning

confidence: 99%

COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.

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“…For instance, NR1D1-a circadian rhythm clock gene-regulates FA formations in fibroblast cultures (Cunningham et al, 2020). Additionally, changes in the mechanical stiffness of the microenvironment are sensed by FA complexes and can lead to both altered circadian rhythmicity in mammary and lung epithelial cell cultures (Yang et al, 2017) and changes in rhythmic Ca 2+ signaling between smooth muscle cells (Stasiak et al, 2020).…”

Section: Biological Rhythms In the Context Of Mechanical Stimulation ...mentioning

confidence: 99%

A trio of biological rhythms and their relevance in rhythmic mechanical stimulation of cell cultures

et al. 2022

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The primary aim of this article is to provide a biological rhythm model based on previous theoretical and experimental findings to promote more comprehensive studies of rhythmic mechanical stimulation of cell cultures, which relates to tissue engineering and regenerative medicine fields. Through an interdisciplinary approach where different standpoints from biology and musicology are combined, we explore some of the core rhythmic features of biological and cellular rhythmic processes and present them as a trio model that aims to afford a basic but fundamental understanding of the connections between various biological rhythms. It is vital to highlight such links since rhythmic mechanical stimulation and its effect on cell cultures are vastly underexplored even though the cellular response to mechanical stimuli (mechanotransduction) has been studied widely and relevant experimental evidence suggests mechanotransduction processes are rhythmic.

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Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells

Cited by 14 publications

References 41 publications

The role of mathematical models in designing mechanopharmacological therapies for asthma

The role of mathematical models in designing mechanopharmacological therapies for asthma

COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases

A trio of biological rhythms and their relevance in rhythmic mechanical stimulation of cell cultures

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