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Identify Bcl3 as a novel biomarker shared between severe asthma and lung cancer using next-generation RNA sequencing from archival FFPE tissue biopsies
Conclusion: Our findings indicate a Bcl3 a novel putative biomarker in pathogeneses of both severe asthma and lung cancer.
Source: European Respiratory Journal - December 1, 2022 Category: Respiratory Medicine Authors: Salameh, L., Manasa Bhamidimarri, P., Elemam, N., Ali, N., Dairi, Y., Alsharhan, M., Tirmazy, S. H., Hamid, Q., Mahboub, B., Al Heialy, S., Hamoudi, R. Tags: 03.03 - Mechanisms of lung injury and repair Source Type: research

6-aminonicotinamide ameliorates pulmonary fibrosis by suppressing the TGF-beta1 activated Smad signalling pathway
Conclusions: Our findings indicate that inhibition of G6PD may have anti-fibrotic effects on pulmonary fibrosis, suggesting that G6PD is implicated as a potential therapeutic target in IPF.Figure: Comparison of hydroxyproline levels in the bleomycin induced lung fibrosis mouse model according to the treatment
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Kim, M., Kim, H.-S., Moon, S.-J., Yoo, H. J., Song, J. W. Tags: Mechanisms of lung injury and repair Source Type: research

Role of c-Abelson in the loss of genome integrity in endothelial cells in pulmonary arterial hypertension
Conclusions: Our results demonstrate a central role of c-Abl in the loss of DNA integrity in iPAH P-ECs.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Le Vely, B., Berrebeh, N., Phan, C., Thuillet, R., Humbert, M., Huertas, A., Guignabert, C., Tu, L. Tags: Pulmonary hypertension Source Type: research

Inhibition of the Arp2/3 complex inhibits lung myofibroblast differentiation in vitro and attenuates bleomycin-induced pulmonary fibrosis in mice
Conclusion: Increased expression of Arp2/3 was observed both in IPF fibroblasts and in bleomycin-exposed mouse lungs. CK666 and siARPC2 attenuated profibrotic differentiation of lung fibroblasts. CK666 attenuated bleomycin-induced lung fibrosis in vivo. Arp2/3 Inhibition may be an attractive new therapy for IPF and other fibrotic interstitial lung diseases.
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Mergault, C., Lisee, F., Tiroille, V., Heuze-VourcH, N., Parent, C., Sizaret, D., Marchand-Adam, S., Plantier, L. Tags: Mechanisms of lung injury and repair Source Type: research

Downregulation of lysosome-associated membrane protein-2A accelerates cigarette smoke extract-induced aging and apoptosis in human bronchial epithelial cells
In this study, we evaluated the expression level of LAMP-2A in lung tissues and primary human bronchial epithelial cells (HBEC) of the normal, smoker, and COPD patients and investigated the role of LAMP-2A in cigarette smoke extract (CSE)-induced aging and death in lung epithelial cells (BEAS-2B). The protein level of LAMP-2A significantly decreased in lung homogenates from smokers and COPD patients compared with never smokers. Immunohistochemical analysis showed a significant decrease of LAMP-2A level in lung epithelial cells. Primary HBEC from smokers and COPD patients expressed a lower level of LAMP-2A than never smoker...
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Lee, K.-H., Jeong, Y., Kim, J. Y., Lee, C.-H., Yoo, C.-G. Tags: Mechanisms of lung injury and repair Source Type: research

Hypoxia-inducible factor pathway activation promotes bone-type collagen cross-linking in Idiopathic Pulmonary Fibrosis
Conclusions: Our results suggest that HIF pathway activation via LH2/LOXL2 may be a core regulator of bone-type collagen fibrillogenesis in IPF.
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Brereton, C. J., Yao, L., Bell, J., Conforti, F., Alzetani, A., Fabre, A., Marshall, B. G., Richeldi, L., Davies, D. E., Wang, Y., Jones, M. G. Tags: Mechanisms of lung injury and repair Source Type: research

Investigating the role of AKAP13 on epithelial cell TGFss activation
Conclusion: AKAP13 expression is found predominantly in epithelial cells in the lung. AKAP13 appears to regulate RhoA activation in iHBECs and influence αvβ6 expression. This suggests that it is involved in the RhoA-αvβ6 pathway that drives TGF-β activation in epithelial cells.
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Organ, L., Porte, J., John, A., Jenkins, G. Tags: Mechanisms of lung injury and repair Source Type: research

FKBP10 regulates fibroblast migration via synthesis of collagen VI
Conclusion: FKBP10 deficiency in phLF attenuates migration mainly by decreased synthesis of collagen VI.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Knüppel, L., Heinzelmann, K., Lindner, M., Hatz, R., Behr, J., Eickelberg, O., Staab-Weijnitz, C. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Role of microtubule-associated signaling in Staphylococcus aureus-induced lung injury.
This study tested the role of microtubules (MT) in the mechanisms of SA-induced ALI. EC dysfunction was accompanied by decrease in acetylated tubulin, MT destabilization, and increased activity of histone deacetylase-6 (HDAC6) as a result of oxidative stress. HDAC6 inhibition using gene-specific siRNA or tubastatin A rescued SA-induced EC barrier disruption monitored by measurements of electrical resistance and macromolecular permeability. SA-induced EC dysfunction was associated with impaired MT-mediated delivery of cytoplasmic linker-associated protein 2 to the cell periphery limiting its interaction with adherens juncti...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Birukova, A., Karki, P., Tian, Y., Sarich, N., Ke, Y., Birukov, K. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis
Conclusion: Intact MKP5 is required for induction of changes in lung fibroblasts in-vitro and during bleomycin-induced lung fibrosis in-vivo. MKP5 inhibition represent a promising therapeutic target for experimental and lung fibrosis.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tzouvelekis, A., Karampitsakos, T., Min, K., Xylourgidis, N., Yu, G., Herazo-Maya, J., Bizenhofer, L., Bennett, A., Kaminski, N. Tags: Idiopathic interstitial pneumonias Source Type: research

Cigarette smoke exposure decreases CFLAR expression in bronchial epithelium, augmenting susceptibility for cell death and DAMP release
In conclusion, CS exposure decreases CFLAR expression, which might increase susceptibility to immunogenic cell death. Our study suggests that susceptibility for CS-induced airway inflammation is driven by dysregulated cell death machinery, which may be used at target for future COPD treatments.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Pouwels, S. D., Faiz, A., Heijink, I. H., Vermeulen, C. J., Guryev, V., Van Den Berge, M., Nawijn, M. C. Tags: Mechanisms of Lung Injury and Repair Source Type: research

MKP-5 inhibition blunts fibrotic responses in-vitro and in-vivo through negative regulation of TGFB1-induced smad3-signalling
Conclusion: We conclude that intact MKP5 is required for induction of changes in lung fibroblasts in-vitro and during bleomycin-induced lung fibrosis in-vivo. Our results couple MKP5 activity with TGFB1 signaling machinery identifying MKP5 inhibition as a promising therapeutic strategy for experimental and human lung fibrosis.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tzouvelekis, A., Xylourgidis, N., Min, K., Karampitsakos, T., Ninou, I., Barbayianni, I., Bennett, A., Aidinis, V., Kaminski, N. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Involvement of GPx4-regulated lipid peroxidation in IPF pathogenesis.
Conclusion: These findings suggest that GPx4 expression levels were reduced in IPF and GPx4-regulated lipid peroxidation can be involved in IPF pathogenesis via modulating TGF-b-induced myofibroblast differentiation.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tsubouchi, K., Araya, J., Minagawa, S., Hara, H., Hosaka, Y., Ichikawa, A., Saito, N., Yoshida, M., Ishikawa, T., Numata, T., Kaneko, Y., Nakayama, K., Kuwano, K. Tags: Mechanisms of Lung Injury and Repair Source Type: research

LSC - 2017 - The role of the epigenetic regulator HMGN5 in COPD resulting from chronic lung injury
COPD, characterized by chronic bronchitis, small airway remodeling and emphysema, is one of the leading causes of chronic morbidity and mortality worldwide. Chronic lung injury, commonly caused by cigarette smoking (CS), is a major factor in its development. A role for epigenetics in this underlying pathology is emerging. We previously detected spontaneous emphysema in HMGN5-/-mice. HMGN5 binds to the nucleosomal core particle of chromatin, competing with histone H1, altering chromatin structure and affecting cellular transcription, differentiation and repair. Indeed, increased expression of HMGN5 has been observed in lung...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Gunes, G., Conlon, T., Sarker, R., Burgstaller, G., Gailus-Durner, V., Fuchs, H., Hrabe de Angelis, M., Furusawa, T., Bustin, M., Eickelberg, O., Önder Yildirim, A., Dorer, J. Tags: Molecular Pathology and Functional Genomics Source Type: research

Transcriptional Profiling reveals Reprogramming of Airway Basal Cells in IPF
Conclusion: airway basal cells derived from distal airways are reprogrammed in IPF which results in malfunction and mislead repair processes.
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Prasse, A., Jäger, B., Carleo, A., Jonigk, D., DeLuca, D. Tags: Mechanisms of Lung Injury and Repair Source Type: research

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