Decreased CCAAT/Enhancer Binding Protein Transcription Factor Activity in Chronic Bronchitis and COPD

Didon, Lukas; Qvarfordt, Ingemar; Andersson, Olof; Nord, Magnus; Riise, Gerdt C.

doi:10.1016/s0012-3692(15)34485-8

Cited by 16 publications

(31 citation statements)

References 19 publications

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“…There is a striking overlap, both in human and mouse lung, in the cellular expression pattern of Nod1 (as observed in the present study) and the C/EBP-transcription factors [17,18,25]. Therefore, the activation of C/EBP family members downstream of Nod1 was further investigated by EMSA using antibodies to C/EBPb and C/EBPd.…”

Section: Activation Of Transcription Factors Downstream Of Nod1supporting

confidence: 74%

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The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein signalling in lung epithelial cells

Barton¹,

Berg²,

Didon³

et al. 2007

European Respiratory Journal

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The innate immune receptor nucleotide-binding oligomerisation domain protein 1 (Nod1) recognises peptidoglycan containing meso-diaminopimelic acid found in all Gramnegative and some Gram-positive bacteria. Nod1 has been shown to activate nuclear factor (NF)-kB. The aim of the present study was to examine the expression of Nod1 in the lung, particularly in lung epithelial cells, and to investigate the activation of CCAAT/enhancer binding protein (C/EBP) transcription factors downstream of the Nod1 receptor in these cells.

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Section: Activation Of Transcription Factors Downstream Of Nod1supporting

confidence: 74%

“…The expression pattern of C/EBPs in the lung has recently been described [17,18,25]. C/EBPb is expressed in airway epithelial cells, as well as alveolar type-II cells and alveolar macrophages, and C/EBPd is found in the airway epithelium and alveolar type-II cells.…”

Section: Discussionmentioning

confidence: 98%

The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein signalling in lung epithelial cells

Barton¹,

Berg²,

Didon³

et al. 2007

European Respiratory Journal

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Section: Discussionmentioning

confidence: 99%

“…A role for C/ EBPs in the regulation of differentiation, proliferation, as well as in inflammation and immunological defenses in other organs and tissues is well established (Poli, 1998;Diamond et al, 2000;Musikacharoen et al, 2001;Ramji and Foka, 2002;Cassel and Nord, 2003), and an increasing amount of evidence implicates C/EBPs in lung diseases (Halmos et al, 2002;Roth et al, 2004;Didon et al, 2005Didon et al, , 2010Didon et al, , 2011Binia et al, 2011). We have previously observed reduced activity of C/EBPb in smokers with chronic obstructive pulmonary disease (COPD) (Didon et al, 2005) as well as reduced expression of C/EBPb in cigarette smokers (Didon et al, 2011), indicating a role for C/ EBPs in COPD pathogenesis. In addition, defective C/EBPa signaling is associated with dysfunctional lung maturation (Basseres et al, 2006;Berg et al, 2006;Martis et al, 2006;Didon et al, 2010), reminiscent of the pulmonary immaturity of premature children with bronchopulmonary dysplasia, which may contribute to obstructive symptoms later in life (Vrijlandt et al, 2006;Lum et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Based on our results, loss of C/EBPs in chronic pulmonary diseases could contribute to mucus cell differentiation. Thus, the impaired C/ EBPb signaling in smokers with or without COPD (Didon et al, 2005(Didon et al, , 2011 prompts additional studies investigating C/EBP signaling in epithelial differentiation. Considering the high lethality of Cebpa DLE mice (Didon et al, 2010), assessment of double C/ EBP deletion in an adult model addressing inflammatory lung diseases would preferably utilize a transgene with lung-specific, inducible Cre.…”

Section: Dlementioning

confidence: 99%

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Airway epithelial cell differentiation during lung organogenesis requires C/EBPα and C/EBPβ

Roos

Berg

Barton

et al. 2012

Developmental Dynamics

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Background: CCAAT/enhancer‐binding protein (C/EBP)α is crucial for lung development and differentiation of the pulmonary epithelium. Conversely, no lung defects have been observed in C/EBPβ‐deficient mice, although C/EBPβ trans‐activate pulmonary genes by binding to virtually identical DNA‐sequences as C/EBPα. Thus, the pulmonary phenotype of mice lacking C/EBPβ could be explained by functional replacement with C/EBPα. We investigated whether C/EBPα and C/EBPβ have overlapping functions in regulating lung epithelial differentiation during organogenesis. Epithelial differentiation was assessed in mice with a lung epithelial–specific (SFTPC‐Cre‐mediated) deletion of C/EBPα (CebpaΔLE), C/EBPβ (CebpbΔLE), or both genes (CebpaΔLE; CebpbΔLE). Results: Both CebpaΔLE mice and CebpaΔLE; CebpbΔLE mice demonstrated severe pulmonary immaturity compared to wild‐type littermates, while no differences in lung histology or epithelial differentiation were observed in CebpbΔLE mice. In contrast to CebpaΔLE mice, CebpaΔLE; CebpbΔLE mice also displayed undifferentiated Clara cells with markedly impaired protein and mRNA expression of Clara cell secretory protein (SCGB1A1), compared to wild‐type littermates. In addition, ectopic mucus‐producing cells were observed in the conducting airways of CebpaΔLE; CebpbΔLE mice. Conclusions: Our findings demonstrate that C/EBPα and C/EBPβ play pivotal, and partly overlapping roles in determining airway epithelial differentiation, with possible implications for tissue regeneration in lung homeostasis and disease. Developmental Dynamics 241:911–923, 2012. © 2012 Wiley Periodicals, Inc.

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Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains

et al. 2015

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BackgroundMouse models are useful for studying cigarette smoke (CS)-induced chronic pulmonary pathologies such as lung emphysema. To enhance translation of large-scale omics data from mechanistic studies into pathophysiological changes, we have developed computational tools based on reverse causal reasoning (RCR).ObjectiveIn the present study we applied a systems biology approach leveraging RCR to identify molecular mechanistic explanations of pathophysiological changes associated with CS-induced lung emphysema in susceptible mice.Methods The lung transcriptomes of five mouse models (C57BL/6, ApoE−/−, A/J, CD1, and Nrf2−/−) were analyzed following 5–7 months of CS exposure.Results We predicted 39 molecular changes mostly related to inflammatory processes including known key emphysema drivers such as NF-κB and TLR4 signaling, and increased levels of TNF-α, CSF2, and several interleukins. More importantly, RCR predicted potential molecular mechanisms that are less well-established, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1, and N-COR, and reduced protein abundance of ITGB6 and CFTR. We corroborated several predictions using targeted proteomic approaches, demonstrating increased abundance of CSF2, C/EBPα, C/EBPβ, PU.1, BRCA1, and STAT1.Conclusion These systems biology-derived candidate mechanisms common to susceptible mouse models may enhance understanding of CS-induced molecular processes underlying emphysema development in mice and their relevancy for human chronic obstructive pulmonary disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00011-015-0820-2) contains supplementary material, which is available to authorized users.

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Decreased CCAAT/Enhancer Binding Protein Transcription Factor Activity in Chronic Bronchitis and COPD

Cited by 16 publications

References 19 publications

The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein signalling in lung epithelial cells

The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein signalling in lung epithelial cells

Airway epithelial cell differentiation during lung organogenesis requires C/EBPα and C/EBPβ

Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains

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