JAK-STAT signaling as an ARDS therapeutic target: Status and future trends

Zhang, Yuanteng; Gao, Zizheng; Jiang, Feng; Yan, Hao; Yang, Bo; He, Qiaojun; Luo, Peihua; Xu, Zhifang; Yang, Xiaochun

doi:10.1016/j.bcp.2022.115382

Cited by 4 publications

(3 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Coronavirus-2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and is characterized by a respiratory illness, multiple organ failure, pneumonia, acute respiratory distress syndrome (ARDS), and finally, death ( Agrawal et al, 2020 ; Jain et al, 2022 ). In addition to these symptoms, patients with this condition exhibit several systemic manifestations, such as lymphopenia, abnormalities of ferritin levels, prothrombin time, platelet count, acute partial thromboplastin time, and blood clotting anomalies ( Zhang et al, 2023 ). SARS-CoV-2-induced senescence of infected cells was reported to be a triggering factor for COVID-19-related cytokine release syndrome and multi-organ failure ( Lee et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

et al. 2023

View full text Add to dashboard Cite

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

show abstract

Section: Introductionmentioning

confidence: 99%

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

et al. 2023

View full text Add to dashboard Cite

show abstract

“…STAT1, STAT3 and STAT5, when activated by granulocyte colony-stimulating factor (G-CSF) promote the accumulation and activation of neutrophils in the lung (Fig. 2 d) [ 90 ]. Excessive activation of these immune cells leads to an unrestrained release of pro-inflammatory cytokines and chemokines, aggravating lung injury [ 91 ].…”

Section: Molecular Mechanisms and Signaling Pathwaysmentioning

confidence: 99%

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Huang,

Le,

et al. 2024

Respir Res

View full text Add to dashboard Cite

Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities with refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With the outbreak of coronavirus disease 19 worldwide, the mortality of ARDS has increased correspondingly. Comprehending the pathophysiology and the underlying molecular mechanisms of ARDS may thus be essential to developing effective therapeutic strategies and reducing mortality. To facilitate further understanding of its pathogenesis and exploring novel therapeutics, this review provides comprehensive information of ARDS from pathophysiology to molecular mechanisms and presents targeted therapeutics. We first describe the pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress. Next, we summarize the molecular mechanisms and signaling pathways related to the above four aspects of ARDS pathophysiology, along with the latest research progress. Finally, we discuss the emerging therapeutic strategies that show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies and mesenchymal stromal cell therapies, highlighting the pathophysiological basis and the influences on signal transduction pathways for their use.

show abstract

“…1 ). The important role of STAT in the regulation of immune response and other biological events has been revealed in gene-targeting studies ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID‑19 (Review)

Li,

Zhuang,

Shao

et al. 2024

Mol Med Rep

View full text Add to dashboard Cite

The intracellular pathway of Janus kinase/signal transducer and activator of transcription (JAK/STAT) and modification of nucleosome histone marks regulate the expression of proinflammatory mediators, playing an essential role in carcinogenesis, antiviral immunity and the interaction of host proteins with Herpesviral particles. The pathway has also been suggested to play a vital role in the clinical course of the acute infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2; known as coronavirus infection-2019), a novel human coronavirus initially identified in the central Chinese city Wuhan towards the end of 2019, which evolved into a pandemic affecting nearly two million people worldwide. The infection mainly manifests as fever, cough, myalgia and pulmonary involvement, while it also attacks multiple viscera, such as the liver. The pathogenesis is characterized by a cytokine storm, with an overproduction of proinflammatory mediators. Innate and adaptive host immunity against the viral pathogen is exerted by various effectors and is regulated by different signaling pathways notably the JAK/STAT. The elucidation of the underlying mechanism of the regulation of mediating factors expressed in the viral infection would assist diagnosis and antiviral targeting therapy, which will help overcome the infection caused by SARS-CoV-2.

show abstract

JAK-STAT signaling as an ARDS therapeutic target: Status and future trends

Cited by 4 publications

References 104 publications

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID‑19 (Review)

Contact Info

Product

Resources

About