Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches

Savin, Innokenty A.; Zenkova, Marina A.; Sen’kova, Aleksandra V.

doi:10.3390/ijms232314959

Cited by 75 publications

(52 citation statements)

References 443 publications

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“…The bleomycin‐induced mouse lung injury model has multiple modes of administration, such as intraperitoneal (ip), intravenous (iv), intratracheal (it), and subcutaneous. Currently, the endotracheal route is the most common route of administration 162–165 . In mouse models, body weight‐based dosing typically ranges from 1.25 to 4 U/kg.…”

Section: Research Models Of Lung Injury and Regenerationmentioning

confidence: 99%

Lung regeneration: diverse cell types and the therapeutic potential

Chen,

Li,

et al. 2024

MedComm

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Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

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Section: Research Models Of Lung Injury and Regenerationmentioning

confidence: 99%

Lung regeneration: diverse cell types and the therapeutic potential

Chen,

Li,

et al. 2024

MedComm

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“…Furthermore, to limit the replication and spread of SARS-CoV-2 in COVID-19 patients, TNF-α also promotes the influx of neutrophils to the respiratory tract. The recruited neutrophils are sensitized by the virus and its antigens and release matrix metalloproteinase (MMP)-9, which is strongly associated with irreversible pulmonary fibrosis in COVID-19 patients [ 72 ].…”

Section: Implication Of Tnf-α Signaling In Covid-19 Mortality and Mor...mentioning

confidence: 99%

Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management

Zawawi

Kalyanasundram

Zain

et al. 2023

IJMS

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The coronavirus disease 2019 (COVID-19) became a worldwide concern at the beginning of 2020 and has affected millions. Several previous studies revealed the impact of the imbalanced innate immune response on the progression of COVID-19 and its disease outcomes. High levels of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins are produced readily by innate immune cells to fight Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Nonetheless, cytokine-mediated inflammatory events are also linked to detrimental lung injury and respiratory failure, which can result in deaths among COVID-19 patients. TNF-α is amongst the early cytokines produced to mediate proinflammatory responses and enhance immune cell infiltration in response to SARS-CoV-2 infections. In COVID-19, TNF-α-mediated inflammation can cause detrimental tissue damage and gradually promotes lung fibrosis, which later results in pneumonia, pulmonary edema, and acute respiratory distress syndrome. This review, therefore, aims to deliberate the immunomodulatory roles of TNF-α in promoting inflammation and its relation with COVID-19 morbidity and mortality. In addition, this review also proposes the potential of TNF-α as a biomarker for the prognosis of severe COVID-19 and its related complications and as a molecular target for anti-TNF-α therapy.

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“…Mechanical ventilation (MV) is often used to maintain life in patients with ARDS. However, despite the widespread use of lung-protective ventilation strategies, ventilator-induced lung injury (VILI), which is characterized by an initial inhomogeneous inflammatory reaction or epithelial injury followed by a fibroproliferative phase with extracellular matrix (ECM) accumulation, continues to occur [ 1 , 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the effective therapeutic approaches for pulmonary fibrosis treatment are still lacking. Therefore, exploring potential molecular mechanisms underlying the transition from acute lung inflammation to pulmonary fibrosis is crucial to facilitating the search for new molecular markers and promising therapeutic targets as well as the transition of patients with ALI away from long-term ventilatory support [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Ventilation-Enhanced Epithelial–Mesenchymal Transition through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model

Huang

et al. 2023

IJMS

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Mechanical ventilation (MV) used in patients with acute lung injury (ALI) induces lung inflammation and causes fibroblast proliferation and excessive collagen deposition—a process termed epithelial–mesenchymal transition (EMT). Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating EMT during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, EMT, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase EMT through the PI3K-γ pathway. C57BL/6 mice, either wild-type or PI3K-γ-deficient, were exposed to 6 or 30 mL/kg MV for 5 h after receiving 5 mg/kg AS605240 intraperitoneally 5 days after bleomycin administration. We found that, after bleomycin exposure in wild-type mice, high-tidal-volume MV induced substantial increases in inflammatory cytokine production, oxidative loads, Masson’s trichrome staining level, positive staining of α-smooth muscle actin, PI3K-γ expression, and bronchial epithelial apoptosis (p < 0.05). Decreased respiratory function, antioxidants, and staining of the epithelial marker Zonula occludens-1 were also observed (p < 0.05). MV-augmented bleomycin-induced pulmonary fibrogenesis and epithelial apoptosis were attenuated in PI3K-γ-deficient mice, and we found pharmacological inhibition of PI3K-γ activity through AS605240 (p < 0.05). Our data suggest that MV augmented EMT after bleomycin-induced ALI, partially through the PI3K-γ pathway. Therapy targeting PI3K-γ may ameliorate MV-associated EMT.

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Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches

Cited by 75 publications

References 443 publications

Lung regeneration: diverse cell types and the therapeutic potential

Lung regeneration: diverse cell types and the therapeutic potential

Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management

Attenuation of Ventilation-Enhanced Epithelial–Mesenchymal Transition through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model

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