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BMI is reduced in COPD
Conclusion: Our results suggest that the absence of BMI1 accelerates senescence in alveolar epithelial cells and promotes COPD formation.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Yao, X., Wu, , Adock, I. Tags: Allergy and immunology Source Type: research

Latent TGF-ss binding protein 4 is an important factor that influences anti-inflammatory and cell-protective responses in the pathogenesis of pulmonary emphysema
Conclusion: Our results suggest a unique function for LTBP-4 that influences anti-inflammatory and cell-protective responses in elastic fiber assembly. These data are potentially useful for the treatment or prevention of pulmonary emphysema.
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Ishii, M., Yamaguchi, Y., Hamaya, H., Iwata, Y., Ogawa, S., Akishita, M. Tags: Airway cell biology and immunopathology Source Type: research

Chromatin dynamics via HMGN5 regulates COPD susceptibility
A role for epigenetics in COPD susceptibility is emerging. We previously detected spontaneous emphysema development in HMGN5 deficient mice. HMGN5 binds to the nucleosomal core particle of chromatin, competing with histone H1, thus altering chromatin structure and function. Here we investigate the contribution of HMGN5 to the development of emphysema.COPD patient lungs were analyzed by RNAseq and immunofluorescence. B6 and Hmgn5-/- mice were treated with porcine pancreatic elastase (PPE, 40U/Kg) and analyzed on d28. siRNA knock-down of Hmgn5 in ATII cells (LA4) was followed by wound healing, apoptosis and cell proliferatio...
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Conlon, T., Dorer, J., Sarker, R., Burgstaller, G., Merthan, L., Gailus-Durner, V., Fuchs, H., Hrabe De Angelis, M., Furusawa, T., Bustin, M., Yildirim, A. O. Tags: Molecular pathology and funct. genomics Source Type: research

The Hippo pathway effectors TAZ and YAP are sequentially required in lung development
Conclusion: Our results indicate that TAZ and YAP function at different stages of lung development in lung epithelial cells and essential for proper lung development. Our results suggested the existence of a novel pathway between TGF-beta and Shh.
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Isago, H., Mitani, A., Kohno, S., Nagoshi, H., Ishimori, T., Saito, M., Tamiya, H., Mikami, Y., Horie, M., Urushiyama, H., Jo, T., Tanaka, G., Hamamoto, R., Terasaki, Y., Nagase, T. Tags: Lung and airway developmental biology 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

Accelerating lung epithelial cell senescence in reduced CARM1 mice enhances elastase-induced emphysema
Emphysema, a key feature of chronic obstructive pulmonary disease is characterized by progressive destruction of pulmonary alveoli. Emphysema development involves alveolar senescence. CARM1, an arginine methyltransferase and transcriptional cofactor, methylating histone and non-histone proteins found crucial for regulating senescence (Wang, BMC Mol Biol 2013). We therefore, hypothesized that loss of CARM1 induces alveolar epithelial cell senescence and thus enhances the susceptibility to elastase-induced emphysema.Porcine pancreatic elastase (PPE) treated C57BL/6 (WT) or CARM1+/- mice were analyzed for lung function, histo...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Sarker, R. S. J., Bohla, A., Amarie, O. V., Eickelberg, O., Yildirim, A. O. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research

Fibroblast-derived non-canonical WNT ligands contribute to attenuated alveolar epithelial repair in COPD
Conclusion: In COPD, attenuated canonical WNT signaling and disturbed alveolar epithelial cell repair may be a consequence of a shift in conditions that triggers WNT-5A secretion by fibroblasts.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Baarsma, H. A., Boczkowski, J., Yildirim, A. O., Konigshoff, M. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research

Reduction of high mobility group nucleosome binding domain-5 protein promotes the development of emphysema
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is associated with an enhanced chronic inflammation and development of emphysema. However, the mechanism by which genetic alteration contributes to empyhsema development is still barely understood. In a previous study we have detected spontaneous emphysema development in HMGN5 knockout mice (Kluger E.J., et. al., JBC 2013). The HMGN5 gene encodes a nucleosomal binding protein that competes with H1 on the nucleosome and loosens the structure of chromatin. It plays an important role in transcription, replication and the repair mechanism...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Merthan, L., Bustin, M., Eickelberg, O., Yildirim, A. O. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research