Pulmonary fibrosis: from pathogenesis to clinical decision-making

Koudstaal, Thomas; Funke-Chambour, Manuela; Kreuter, Michael; Molyneaux, Philip L.; Wijsenbeek, Marlies S.

doi:10.1016/j.molmed.2023.08.010

Cited by 21 publications

(14 citation statements)

References 99 publications

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“…Mrc1 is a type I transmembrane protein expressed on the surface of various immune cells, including alveolar macrophages [41]. It acts as a pattern recognition receptor, recognizing and binding to microbial pathogens that invaded lungs [2,41]. Mrc1 has been shown to have immunoregulatory functions by promoting anti-inflammatory and tissue repair responses.…”

Section: Msc-exo-dependent Suppression Of Immune Cells In Fibrotic Lungsmentioning

confidence: 99%

“…Lung or pulmonary fibrosis is a chronic and progressive lung disease characterized by the formation of excessive scar tissue, fibrosis, in the lungs [1]. This scarring occurs due to the abnormal accumulation of collagen and other extracellular matrix components, which leads to the thickening and stiffening of lung parenchymal [1,2]. The pathological process begins with an initial insult or injury to the lung, which can be caused by various factors such as environmental toxins, infections, autoimmune reaction or radiation exposure [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…This scarring occurs due to the abnormal accumulation of collagen and other extracellular matrix components, which leads to the thickening and stiffening of lung parenchymal [1,2]. The pathological process begins with an initial insult or injury to the lung, which can be caused by various factors such as environmental toxins, infections, autoimmune reaction or radiation exposure [2,3]. Alarmins and damage-associated molecular patterns (DAMPs), released from injured cells, bind to their receptors on the membrane of lung-infiltrated immune cells, leading to their activation [4].…”

Section: Introductionmentioning

confidence: 99%

“…Upon DAMPs-dependent activation, alveolar macrophages produce TNF-α and IL-1β (which induce enhanced expression of E and P selectins on lung endothelial cells (ECs)) and neutrophil-, monocyte-and T cellattracting chemokines (CCL2, CCL3 and CXCL12) which bind to their respective receptors on circulating leukocytes, enabling their massive influx in the fibrotic areas [4,5]. As a result, the lungs become infiltrated with immune cells, less elastic and unable to properly expand [1,2].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanisms Responsible for the Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Lung Fibrosis

Harrell,

Djonov,

Volarevic

et al. 2024

IJMS

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Mesenchymal stem cell-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain various MSC-sourced anti-fibrotic, immunoregulatory and angio-modulatory proteins (growth factors, immunoregulatory cytokines, chemokines), lipids, and nucleic acids (messenger RNA and microRNAs). Due to their lipid envelope, MSC-Exos easily by-pass all barriers in the body and deliver their cargo directly in target cells, modulating their viability, proliferation, phenotype and function. The results obtained in recently published experimental studies demonstrated beneficial effects of MSC-Exos in the treatment of lung fibrosis. MSC-Exos reduced activation of fibroblasts and prevented their differentiation in myofibroblasts. By delivering MSC-sourced immunoregulatory factors in lung-infiltrated monocytes and T cells, MSC-Exos modulate their function, alleviating on-going inflammation and fibrosis. MSC-Exos may also serve as vehicles for the target delivery of anti-fibrotic and immunomodulatory agents, enabling enhanced attenuation of lung fibrosis. Although numerous pre-clinical studies have demonstrated the therapeutic potential of MSC-Exos in the treatment of pulmonary fibrosis, there are several challenges that currently hinder their clinical implementation. Therefore, in this review article, we summarized current knowledge and we discussed future perspectives regarding molecular and cellular mechanisms which were responsible for the anti-fibrotic, anti-inflammatory and immunoregulatory properties of MSC-Exos, paving the way for their clinical use in the treatment of lung fibrosis.

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Section: Msc-exo-dependent Suppression Of Immune Cells In Fibrotic Lungsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Mechanisms Responsible for the Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Lung Fibrosis

Harrell,

Djonov,

Volarevic

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…In addition, an observational study also showed that each 10 °F (5.6 °C) increase in daily temperature was associated with a 4.3% increase in same-day emergency hospitalizations for respiratory diseases [ 9 ]. Lung fibrosis is a progressive, chronic lung disease characterized by interstitial inflammation, disrupted alveolar structure, fibroblast proliferation and the excessive accumulation of extracellular matrix (ECM) [ 10 ]. Pulmonary interstitial inflammation is usually an early event in the development of lung fibrosis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence

Hou,

Zhang,

Wang

et al. 2024

IJMS

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It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-β1 (TGF-β1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial–mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated β-galactosidase (SA-β-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS–STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS–STING pathway followed by cellular senescence.

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