Regulation of lung sufactant protein gene expression

Boggaram, Vijayakumar

doi:10.2741/1062

Cited by 66 publications

(21 citation statements)

References 186 publications

(162 reference statements)

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“…In parallel with SP expression, we evaluated by Western blot the expression of TTF1, a transcription factor known to play a major role in various aspects of fetal lung development, including as a positive regulator of surfactant–protein gene-promoter activity [39]. Consistent with our findings on SP expression, at no stage was any obvious difference found between fetuses with CDH and control fetuses (Figure 3).…”

Section: Resultssupporting

confidence: 70%

“…No developmental change was observed for proSP-C because it does not accumulate in the developing lung, unlike mature proteins [43]. Considering the role of TTF1 as a transcription regulator of SPs [39], the absence of any change in SP content is fully consistent with unchanged TTF1 protein abundance between CDH and control lungs, and with the comparable staining for TTF1 that has been observed previously [44]. …”

Section: Discussionsupporting

confidence: 59%

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Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

et al. 2007

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BackgroundPulmonary hypoplasia and persistent pulmonary hypertension account for significant mortality and morbidity in neonates with congenital diaphragmatic hernia (CDH). Global lung immaturity and studies in animal models suggest the presence of surfactant deficiency that may further complicate the pathophysiology of CDH. However, data about surfactant status in human fetuses with CDH at birth are contradictory. The lack of a chronological study of surfactant content in late pregnancy has been a significant limitation. The appropriateness of administering surfactant supplements to neonates with CDH is therefore a debated question.Methods and FindingsWe investigated surfactant content in human fetuses with CDH compared to age-matched fetuses with nonpulmonary diseases used as controls. Concentrations of disaturated phosphatidylcholine and surfactant proteins were found to be similar at a given stage of pregnancy, with both components showing a similar pattern of increase with progressing pregnancy in fetuses with CDH and in control fetuses. Thyroid transcription factor 1, a critical regulator of surfactant protein transcription, similarly displayed no difference in abundance. Finally, we examined the expression of three glucocorticoid-regulated diffusible mediators involved in lung epithelial maturation, namely: keratinocyte growth factor (KGF), leptin, and neuregulin 1 beta 1 (NRG1-β1). KGF expression decreased slightly with time in control fetuses, but remained unchanged in fetuses with CDH. Leptin and NRG1-β1 similarly increased in late pregnancy in control and CDH lungs. These maturation factors were also determined in the sheep fetus with surgical diaphragmatic hernia, in which surfactant deficiency has been reported previously. In contrast to the findings in humans, surgical diaphragmatic hernia in the sheep fetus was associated with decreased KGF and neuregulin expression. Fetoscopic endoluminal tracheal occlusion performed in the sheep model to correct lung hypoplasia increased leptin expression, partially restored KGF expression, and fully restored neuregulin expression.ConclusionsOur results indicate that CDH does not impair surfactant storage in human fetuses. CDH lungs exhibited no trend toward a decrease in contents, or a delay in developmental changes for any of the studied surfactant components and surfactant maturation factors. Surfactant amounts are likely to be appropriate to lung size. These findings therefore do not support the use of surfactant therapy for infants with CDH. Moreover, they raise the question of the relevance of CDH animal models to explore lung biochemical maturity.

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Section: Resultssupporting

confidence: 70%

Section: Discussionsupporting

confidence: 59%

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

et al. 2007

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“…The highest overexpression of Nkx2.1 in transgenic mice causes severe pulmonary inflammation, fibrosis, and respiratory failure, associated with eosinophil infiltration and increased eotaxin and IL-6 expression (Wert et al , 2002). Nkx2.1 signaling is critical for surfactant protein, T1a , and CC10 gene expression (Boggaram, 2003; Bruno et al , 1995; Guazzi et al , 1990; Ramirez et al , 1997; Whitsett and Glasser, 1998; Yan et al , 1995; Zhang et al , 1997). Nkx2.1 -deficient pulmonary epithelial cells fail to express nonciliated marker genes, including differentiated Sp-B , Sp-C , and CC10.…”

Section: Molecular Embryology Of the Lungmentioning

confidence: 99%

Lung Organogenesis

Warburton

El-Hashash

Carraro

et al. 2010

Current Topics in Developmental Biology

398

381

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Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and mortality worldwide. Understanding how the lung develops holds the promise that investigators can use this knowledge to aid lung repair and regeneration. In the decade since the “molecular embryology” of the lung was first comprehensively reviewed, new challenges have emerged—and it is on these that we focus the current review. Firstly, there is a critical need to understand the progenitor cell biology of the lung in order to exploit the potential of stem cells for the treatment of lung disease. Secondly, the current familiar descriptions of lung morphogenesis governed by growth and transcription factors need to be elaborated upon with the reinclusion and reconsideration of other factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer detail of lung bud signaling may need to be combined with broader consideration of overarching mechanisms that may be therapeutically easier to target: in this arena, we advance the proposal that looking at the lung in general (and branching in particular) in terms of clocks may yield unexpected benefits.

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“…In contrast to larger bronchioles which are dominated by ciliated and goblet cells, terminal bronchioles lack submucosal glands and are enriched for club cells (formerly known as Clara cells, [8]). Instead of mucus, club cells are secretory cells that produce a form of pulmonary surfactant containing surfactant protein A (SP-A), SP-B and Club Cell specific protein 10 (CC-10) [9]. The surfactant produced by club cells differs from surfactant produced by alveolar epithelial cells, which lacks CC-10 but instead contains SP-C and therefore has different surface active properties [10].…”

Section: Multiplicity Of Epithelial Cells Lining the Respiratory Tmentioning

confidence: 99%

Claudins: Gatekeepers of lung epithelial function

Schlingmann

Molina

Koval

2015

Seminars in Cell & Developmental Biology

155

108

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The lung must maintain a proper barrier between airspaces and fluid filled tissues in order to maintain lung fluid balance. Central to maintaining lung fluid balance are epithelial cells which create a barrier to water and solutes. The barrier function of these cells is mainly provided by tight junction proteins known as claudins. Epithelial barrier function varies depending on the different needs within the segments of the respiratory tree. In the lower airways, fluid is required to maintain mucociliary clearance, whereas in the terminal alveolar airspaces a thin layer of surfactant enriched fluid lowers surface tension to prevent airspace collapse and is critical for gas exchange. As the epithelial cells within the segments of the respiratory tree differ, the composition of claudins found in these epithelial cells is also different. Among these differences is claudin-18 which is uniquely expressed by the alveolar epithelial cells. Other claudins, notably claudin-4 and claudin-7, are more ubiquitously expressed throughout the respiratory epithelium. Claudin-5 is expressed by both pulmonary epithelial and endothelial cells. Based on in vitro and in vivo model systems and histologic analysis of lungs from human patients, roles for specific claudins in maintaining barrier function and protecting the lung from the effects of acute injury and disease are being identified. One surprising finding is that claudin-18 and claudin-4 control lung cell phenotype and inflammation beyond simply maintaining a selective paracellular permeability barrier. This suggests claudins have more nuanced roles for the control of airway and alveolar physiology in the healthy and diseased lung.

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Regulation of lung sufactant protein gene expression

Cited by 66 publications

References 186 publications

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

Lung Organogenesis

Claudins: Gatekeepers of lung epithelial function

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