Regulation of Clara cell secretory protein gene expression by the CCAAT-binding factor NF-Y

Acosta, Adriana; Zariñán, Teresa; Macías, Héctor Corominas; Pasapera, Ana M.; Pérez‐Solis, Marco Allán; Olivares, Aleida; Ulloa‐Aguirre, Alfredo; Gutiérrez-Sagal, Rubén

doi:10.1016/j.abb.2006.11.013

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…Regulation of CCSP gene transcription is incompletely understood; however, positive and negative regulators have been identified, and changes in their activity might also contribute to reduced CCSP production in disease. 1 Although only a small number of animals were assessed in this study-which must therefore be considered a pilot study with limited statistical power-the findings, nevertheless, strongly suggest that reduced CCSP in lung lavage fluid may be a sensitive indicator of epithelial health in the lung of horses, as in other species. 3,29 While this study was restricted to assessment of CCSP in a noninfectious inflammatory lung condition of horses, it is quite possible that reduction in CCSP also occurs in infectious and other pneumonia and may therefore be a marker of chronic lung inflammation.…”

Section: Discussionmentioning

confidence: 83%

Clara Cell Secretory Protein Is Reduced in Equine Recurrent Airway Obstruction

et al. 2009

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Abstract. Horses are prone to recurrent airway obstruction (RAO), an inflammatory lung disease induced by repeated exposure to environmental mold, dust, and bacterial components. Active disease manifests with mucus hyperproduction, neutrophilic inflammation, bronchoconstriction, and coughing. Chronically affected animals have lung remodeling characterized by smooth muscle hyperplasia, collagen deposition, lymphoid hyperplasia, and impaired aerobic performance. Clara cell secretory protein (CCSP) counters inflammation in the lung, hence we hypothesized that CCSP depletion is a key feature of RAO in horses. Recombinant equine CCSP and specific antiserum were produced, and percutaneous lung biopsies were obtained from 3 healthy horses and from 3 RAO-affected horses before and after induction of RAO. CCSP relative gene expression in tissue, as well as protein concentration in lung lavage fluid, was determined. Immunocytochemical analysis, using both light and immunogold ultrastructural methods, demonstrated reduced CCSP staining in lung tissue of animals with RAO.Immunogold label in Clara cell granules was less in animals with chronic RAO than in normal animals, and absent in animals that had active disease. Median lung lavage CCSP concentration was 132 and 129 ng/ml in healthy horses, and 62 and 24 ng/ml in RAO horses before and after challenge, respectively. CCSP lung gene expression was significantly higher in healthy animals than in animals with chronic RAO. Together, these preliminary findings suggest that reduced production of CCSP and subcellular changes in Clara cells are features of chronic environmentally induced lung inflammation in horses.

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Section: Discussionmentioning

confidence: 83%

Clara Cell Secretory Protein Is Reduced in Equine Recurrent Airway Obstruction

et al. 2009

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“…The H441 cell line was isolated from a human lung adenocarcinoma and has been previously used to identify cisacting elements and trans-acting factors implicated in the regulation of lung-specific genes [19,20]. Luciferase reporters driven by various regions of the nFSHR promoter were transiently transfected into the above mentioned cell lines and their activities were compared to those of similar 129/J constructs (based upon homology).…”

Section: Comparative Analysis Of the Fshr Promoter Activitymentioning

confidence: 99%

Molecular cloning and functional analysis of the FSH receptor gene promoter from the volcano mouse (Neotomodon alstoni alstoni)

Pérez‐Solis

Macías

Acosta-MontesdeOca

et al. 2009

Endocr

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To gain further insights on the genetic divergence and the species-specific characteristics of the follicle-stimulating hormone receptor (FSHR), we cloned 946 bp of the 5'-flanking region of the FSHR gene from the volcano mouse (Neotomodon alstoni alstoni), and compared its features with those from other mammalian species. The sequence of neotomodon FSHR (nFSHR) gene from the translation initiation site to -946 is 74, 71, 64, and 59% homologous to rat, mouse (129/J), human, and sheep, respectively. The nFSHR 5'-flanking region exhibits new interesting putative cis-regulatory elements including those for the SRY transcription factor, which had not been previously related to the FSHR gene. The transcriptional regulation properties of nFSHR gene were studied in mouse Sertoli (MSC-1) and non-Sertoli (H441) cell lines, and compared with those obtained with similar 129/J constructs. All constructs tested were more active in H441 than in MSC-1 cells. The low transcription levels detected in MSC-1 cells probably reflect the recruitment of Sertoli cells-specific nuclear factors that repress transcription of the FSHR gene. In H441 cells, 129/J constructs were more active than their neotomodon counterparts, indicating important species-specific differences in their transcription pattern. Functional analysis of a series of progressive 5'-deletion mutants identified regions involved in positive and negative transcriptional regulation as well as the strongest minimal promoter spanning 260 bp upstream the translation initiation site. The identification of inhibitory nuclear transcription factors, which are apparently expressed in MSC-1 cells, may contribute to a better understanding of the transcriptional regulation of the FSHR gene.

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CCSPG38A polymorphism environment interactions regulate CCSP levels differentially in COPD

Knabe

Varilh

Bergougnoux

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Impaired airway homeostasis in chronic obstructive pulmonary disease (COPD) could be partly related to club cell secretory protein (CCSP) deficiency. We hypothesize that CCSP G38A polymorphism is involved and aim to examine the influence of the CCSP G38A polymorphism on CCSP transcription levels and its regulatory mechanisms. CCSP genotype and CCSP levels in serum and sputum were assessed in 66 subjects with stable COPD included in a 1-yr observational study. Forty-nine of them had an exacerbation. In an in vitro study, the impact on the CCSP promoter of 38G wild-type or 38A variant was assessed. BEAS-2B cells were transfected by either the 38G or 38A construct, in the presence/absence of cigarette smoke extract (CSE) or lipopolysaccharides (LPS). Cotransfections with modulating transcription factors, p53 and Nkx2.1, identified by in silico analysis by using ConSite and TFSEARCH were conducted. A allele carrier COPD patients had lower serum and sputum CCSP levels, especially among active smokers, and a decreased body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) score. In vitro, baseline CCSP transcription levels were similar between the wild and variant constructs. CSE decreased more profoundly the CCSP transcription level of 38A transfected cells. The opposite effect was observed with p53 cotransfection. LPS stimulation induced CCSP repression in 38A promoter transfected cells. Cotransfection with Nkx2.1 significantly activated the CCSP promoters irrespective of the polymorphism. Circulating CCSP levels are associated with smoking and the CCSP G38A polymorphism. CSE, LPS, and the Nkx2.1 and p53 transcription factors modulated the CCSP promoter efficiency. The 38A polymorphism exaggerated the CCSP repression in response to p53 and CSE.

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Regulation of Clara cell secretory protein gene expression by the CCAAT-binding factor NF-Y

Cited by 3 publications

References 25 publications

Clara Cell Secretory Protein Is Reduced in Equine Recurrent Airway Obstruction

Clara Cell Secretory Protein Is Reduced in Equine Recurrent Airway Obstruction

Molecular cloning and functional analysis of the FSH receptor gene promoter from the volcano mouse (Neotomodon alstoni alstoni)

CCSPG38A polymorphism environment interactions regulate CCSP levels differentially in COPD

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