Potential Role of Cellular Senescence in Asthma

Wang, Zhao‐Ni; Su, Ruonan; Yang, Bi-Yuan; Yang, Kexin; Yang, Lei; Yan, Yan; Chen, Zhuang‐Gui

doi:10.3389/fcell.2020.00059

Cited by 35 publications

(31 citation statements)

References 175 publications

(268 reference statements)

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“…Recent findings by Chatterjee et al [71] confirmed that elevated androgen levels play a protective role. The present study is in agreement with the findings of Wang et al [72], demonstrating potential implications of senescence along with aging in declining male fertility. Episode-like pulse testosterone supplementation therapy induces tumor senescence and growth arrest down-modulating androgen receptors through its effect on ERK1/2 signaling [73].…”

Section: Discussionsupporting

confidence: 94%

Implication of Membrane Androgen Receptor (ZIP9) in Cell Senescence in Regressed Testes of the Bank Vole

Profaska-Szymik

Gałuszka

Korzekwa

et al. 2020

IJMS

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Here, we studied the impact of exposure to short daylight conditions on the expression of senescence marker (p16), membrane androgen receptor (ZIP9) and extracellular signal-regulated kinase (ERK 1/2), as well as cyclic AMP (cAMP) and testosterone levels in the testes of mature bank voles. Animals were assigned to groups based on an analysis of testis diameter, weight, seminiferous tubule diameter and the interstitial tissue area: group 1, not fully regressed (the highest parameters); group 2 (medium parameters); or group 3, regressed (the lowest parameters). Cells positive for p16 were observed only in the seminiferous tubule epithelium. However, in groups 1 and 2, these were mostly cells sloughed into the tubule lumen. In group 3, senescent cells resided in between cells of the seminiferous epithelium. Staining for ZIP9 was found in Sertoli cells. Western blot analysis showed a trend towards a decreased expression of p16 and ZIP9 in the testes of the voles in groups 2 and 3, compared to group 1. In addition, a trend towards an increased expression of ERK, as well as an increase of cAMP and testosterone levels, was revealed in group 2. In the regressed testes, a functional link exists between senescence and androgen levels with implication of ZIP9 and cAMP/ERK signaling pathways.

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Section: Discussionsupporting

confidence: 94%

Implication of Membrane Androgen Receptor (ZIP9) in Cell Senescence in Regressed Testes of the Bank Vole

Profaska-Szymik

Gałuszka

Korzekwa

et al. 2020

IJMS

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“…In line with this, there is a need to investigate the therapeutic options of inhibiting either the release or activity of ECM DAMPs in fibrosis. DAMPs, have been well characterised in terms of their role in inflammaging, particularly RAGE ligands, which have a well characterised role in innate immune driven pathologies such as COPD, OA and asthma [248][249][250][251]. However, the contribution of DAMPs and the effect of targeting this therapeutically in fibrosis is less well explored.…”

Section: Targeting Senescence As a Potential Therapeutic Approach For The Treatment Of Fibrotic Diseasementioning

confidence: 99%

Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases

et al. 2020

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The extracellular matrix (ECM) is a complex network of macromolecules surrounding cells providing structural support and stability to tissues. The understanding of the ECM and the diverse roles it plays in development, homoeostasis and injury have greatly advanced in the last three decades. The ECM is crucial for maintaining tissue homoeostasis but also many pathological conditions arise from aberrant matrix remodelling during ageing. Ageing is characterised as functional decline of tissue over time ultimately leading to tissue dysfunction, and is a risk factor in many diseases including cardiovascular disease, diabetes, cancer, dementia, glaucoma, chronic obstructive pulmonary disease (COPD) and fibrosis. ECM changes are recognised as a major driver of aberrant cell responses. Mesenchymal cells in aged tissue show signs of growth arrest and resistance to apoptosis, which are indicative of cellular senescence. It was recently postulated that cellular senescence contributes to the pathogenesis of chronic fibrotic diseases in the heart, kidney, liver and lung. Senescent cells negatively impact tissue regeneration while creating a pro-inflammatory environment as part of the senescence-associated secretory phenotype (SASP) favouring disease progression. In this review, we explore and summarise the current knowledge around how aberrant ECM potentially influences the senescent phenotype in chronic fibrotic diseases. Lastly, we will explore the possibility for interventions in the ECM–senescence regulatory pathways for therapeutic potential in chronic fibrotic diseases.

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“…Animal models of SARS-CoV pathogenesis corroborating the age-related susceptibility to COVID-19 disease have demonstrated that the age-driven remodeling of the immune response (i.e., immunosenescence) could play a central role in the enhanced susceptibility of the elderly to the severity and lethality of SARS-CoV-2 infection [ 88 , 89 ]. In addition to immunosenescence, other cellular senescence phenomena in lung-epithelial and -mesenchymal cells might promote chronic airway remodeling and sustain chronic airway inflammation through the well-known capacity of senescent cells to produce large amounts of inflammatory cytokines (e.g., IL-6) as a result of the senescence-associated secretory phenotype (SASP) [ 90 , 91 ]. As the SASP could augment cellular senescence in surrounding cells, such a vicious feedback loop certainly generates a pathogenic condition to infections with viruses that can cause a very brisk cytokine reaction such as SARS-CoV-2.…”

Section: Silibinin and Sars-cov-2: An Early-intervention In Older mentioning

confidence: 99%

Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients

Bosch-Barrera

Martín-Castillo

Buxó

et al. 2020

JCM

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COVID-19, the illness caused by infection with the novel coronavirus SARS-CoV-2, is a rapidly spreading global pandemic in urgent need of effective treatments. Here we present a comprehensive examination of the host- and virus-targeted functions of the flavonolignan silibinin, a potential drug candidate against COVID-19/SARS-CoV-2. As a direct inhibitor of STAT3—a master checkpoint regulator of inflammatory cytokine signaling and immune response—silibinin might be expected to phenotypically integrate the mechanisms of action of IL-6-targeted monoclonal antibodies and pan-JAK1/2 inhibitors to limit the cytokine storm and T-cell lymphopenia in the clinical setting of severe COVID-19. As a computationally predicted, remdesivir-like inhibitor of RNA-dependent RNA polymerase (RdRp)—the central component of the replication/transcription machinery of SARS-CoV-2—silibinin is expected to reduce viral load and impede delayed interferon responses. The dual ability of silibinin to target both the host cytokine storm and the virus replication machinery provides a strong rationale for the clinical testing of silibinin against the COVID-19 global public health emergency. A randomized, open-label, phase II multicentric clinical trial (SIL-COVID19) will evaluate the therapeutic efficacy of silibinin in the prevention of acute respiratory distress syndrome in moderate-to-severe COVID-19-positive onco-hematological patients at the Catalan Institute of Oncology in Catalonia, Spain.

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Potential Role of Cellular Senescence in Asthma

Cited by 35 publications

References 175 publications

Implication of Membrane Androgen Receptor (ZIP9) in Cell Senescence in Regressed Testes of the Bank Vole

Implication of Membrane Androgen Receptor (ZIP9) in Cell Senescence in Regressed Testes of the Bank Vole

Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases

Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients

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