<scp>VEGF</scp> synthesis is induced by prostacyclin and <scp>TGF</scp>‐β in distal lung fibroblasts from <scp>COPD</scp> patients and control subjects: <scp>I</scp>mplications for pulmonary vascular remodelling

Westergren‐Thorsson, Gunilla; Bagher, Mariam; Andersson-Sjöland, Annika; Thiman, Lena; Löfdahl, Claes Gor̈an; Hällgren, Oskar; Bjermer, Leif; Larsson‐Callerfelt, Anna Karin

doi:10.1111/resp.13142

Cited by 32 publications

(25 citation statements)

References 41 publications

(111 reference statements)

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“…Interestingly, VEGF is synthesised in high amounts by distally derived lung fibroblasts and induced by both prostacyclin and TGF-β. In a recent study, synthesised VEGF acted in an autocrine fashion by increasing ECM synthesis, migration and proliferation of human lung fibroblasts [169]. However, in this study there were no significant differences in synthesised VEGF levels between fibroblasts from non-smoking control subjects and those from patients with severe COPD.…”

Section: Angiogenesiscontrasting

confidence: 77%

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Eapen

Hansbro

Larsson‐Callerfelt

et al. 2018

Drugs

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COPD and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking, and exert a considerable societal burden. People suffering from COPD are at a higher risk of developing lung cancer than those without COPD and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower post-operative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we shall provide a detailed overview of possible underlying factors that link COPD and lung cancer and current therapeutic advances from both human and pre-clinical animal models that can effectively mitigate this unholy relationship. Running head-COPD and lung cancer: understanding and treatments

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Section: Angiogenesiscontrasting

confidence: 77%

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Eapen

Hansbro

Larsson‐Callerfelt

et al. 2018

Drugs

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“…Phenotypically different fibroblasts have been reported in central airways and lung parenchyma in COPD [99]. Fibroblasts in the parenchymal tissue were more sensitive to TGFβ1 expression than in the central airways, which resulted in increased VEGF synthesis, proliferation and increased the synthesis of perlecan [99,100]. Fibrotic cells from biopsies taken from patients with asthmatic symptoms showed an increased secretion of perlecan in culture media compared to cells from normal patients [101].…”

Section: Lungmentioning

confidence: 99%

The multifaceted roles of perlecan in fibrosis

et al. 2018

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Perlecan, or heparan sulfate proteoglycan 2 (HSPG2), is a ubiquitous heparan sulfate proteoglycan that has major roles in tissue and organ development and wound healing by orchestrating the binding and signaling of mitogens and morphogens to cells in a temporal and dynamic fashion. In this review, its roles in fibrosis are reviewed by drawing upon evidence from tissue and organ systems that undergo fibrosis as a result of an uncontrolled response to either inflammation or traumatic cellular injury leading to an over production of a collagen-rich extracellular matrix. This review focuses on examples of fibrosis that occurs in lung, liver, kidney, skin, kidney, neural tissues and blood vessels and its link to the expression of perlecan in that particular organ system.

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“…Moreover, the bronchial epithelial cells also discharge transforming growth factor-β (TGFβ), which triggers fibroblast proliferation for tissue remodeling [14,31]. Therefore, small airway-wall remodeling strongly contributes to airflow limitation in COPD, decline in lung function, and poor responses to available therapies [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells

et al. 2020

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COPD is a prevalent lung disease with significant impacts on public health. Affected airways exhibit pulmonary neutrophilia and consequent secretion of pro-inflammatory cytokines and proteases, which result in lung emphysema. Probiotics act as nonspecific modulators of the innate immune system that improve several inflammatory responses. To investigate the effect of Lactobacillus rhamnosus (Lr) on cigarette smoke (CS)-induced COPD C57Bl/6 mice were treated with Lr during the week before COPD induction and three times/week until euthanasia. For in vitro assays, murine bronchial epithelial cells as well as human bronchial epithelial cells exposed to cigarette smoke extract during 24 hours were treated with Lr 1 hour before CSE addition. Lr treatment attenuated the inflammatory response both in the airways and lung parenchyma, reducing inflammatory cells infiltration and the production of proinflammatory cytokines and chemokines. Also, Lr-treated mice presented with lower metalloproteases in lung tissue and lung remodeling. In parallel to the reduction in the expression of TLR2, TLR4, TLR9, STAT3, and NF-κB in lung tissue, Lr increased the levels of IL-10 as well as SOCS3 and TIMP1/2, indicating the induction of an anti-inflammatory environment. Similarly, murine bronchial epithelial cells as well as human bronchial epithelial cells (BEAS) exposed to CSE produced pro-inflammatory cytokines and chemokines, which were inhibited by Lr treatment in association with the production of anti-inflammatory molecules. Moreover, the presence of Lr also modulated the expression of COPD-associated transcription found into BALF of COPD mice group, i.e., Lr downregulated expression of NF-κB and STAT3, and inversely upregulated increased expression of SOCS3. Thus, our findings indicate that Lr modulates the balance between pro-and anti-inflammatory cytokines in human bronchial epithelial cells upon CS exposure and it can be a useful tool to improve the lung inflammatory response associated with COPD.

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VEGF synthesis is induced by prostacyclin and TGF‐β in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling

Abstract: Background and objective: Involvement of pulmonary vascular remodelling is a characteristic sign in COPD.

Cited by 32 publications

References 41 publications

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

The multifaceted roles of perlecan in fibrosis

Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells

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