Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung.

Liley, Helen; White, Roger; Warr, Rg; Benson, Bradley J.; Hawgood, Samuel; Ballard, Philip L.

doi:10.1172/jci114000

Cited by 165 publications

(105 citation statements)

References 35 publications

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“…Genes with these attributes possess expression profiles that were largely increasing from 53 to 140 dpc. Although the production of surfactant is associated with later gestational development, our observations that these surfactant proteins are expressed relatively early in fetal lung development is consistent with a prior description of SFTPB and SFTPC expression as early as Week 13 in humans (30) and before the end of the pseudoglandular stage in mice (31). The early expression of surfactant proteins may also indicate a necessity of early molecular programming of the lung for subsequent development.…”

Section: Discussionsupporting

confidence: 91%

Transcriptomic Analysis of Human Lung Development

Kho

Bhattacharya

Tantisira

et al. 2010

Am J Respir Crit Care Med

110

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Rationale: Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies. Objectives: To define global patterns of gene expression during human lung development. Methods: Genome-wide expression profiling was used to measure the developing lung transcriptome in RNA samples derived from 38 normal human lung tissues at 53 to 154 days post conception. Principal component analysis was used to characterize global expression variation and to identify genes and bioontologic attributes contributing to these variations. Individual gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction analysis. Measurements and Main Results: Gene expression analysis identified attributes not previously associated with lung development, such as chemokine-immunologic processes. Lung characteristics attributes (e.g., surfactant function) were observed at an earlier-than-anticipated age. We defined a 3,223 gene developing lung characteristic subtranscriptome capable of describing a majority of the process. In gene expression space, the samples formed a time-contiguous trajectory with transition points correlating with histological stages and suggesting the existence of novel molecular substages. Induction of surfactant gene expression characterized a pseudoglandular ''molecular phase'' transition. Individual gene expression patterns were independently validated. We predicted the age of independent human lung transcriptome profiles with a median absolute error of 5 days, supporting the validity of the data and modeling approach. Conclusions: This study extends our knowledge of key gene expression patterns and bioontologic attributes underlying early human lung developmental processes. The data also suggest the existence of molecular phases of lung development.

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Section: Discussionsupporting

confidence: 91%

Transcriptomic Analysis of Human Lung Development

Kho

Bhattacharya

Tantisira

et al. 2010

Am J Respir Crit Care Med

110

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“…The mRNA is detected as a single transcript in human fetal lung in as early as 12 wk of gestation, and levels increase throughout the second trimester, reaching~5 0% of the adult level at 24 wk (7). The gene is expressed in alveolar type II and bronchi olar Clara cells of adult lung but not in other tissues (7,8). SP-B gene expression is increased by glucocorticoids and cAMP in cultured explants of rat and human lung, and by in vivo glucocorticoid treatment in fetal rats and rabbits (1, 7, 9 -11).…”

Section: Abstragtmentioning

confidence: 99%

“…Total RNA was isolat ed from lung tissue and specific mRN A content determined by cDNA hybridization using a dot blot apparatus as previously described (7,13). The cDNA probes were labeled with eZp jdCTP using a random prim er labeling technique (oligo labeling kit; Pharma cia Biotech Inc. , Piscataway, NJ).…”

Section: Mrna Contentmentioning

confidence: 99%

Surfactant Protein B in Human Fetal Lung: Developmental and Glucocorticoid Regulation

et al. 1995

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ABSTRAGT Vol. 38, No.5, 1995 Printed ill U.S.A.Pulm onary surfac tant protein B (SP-B) enhances phospholip id film formation in vitro and is essential for normal surfactant functio n in vivo. We examined hum an fetal lung before and during explant culture for content and cellular localization of SP-B mRNA and prote in. SP-B mRNA was low in preculture specime ns (18 -20 wk) but hybridization signal increased ove r epithelial cells dur ing culture and was enha nced by dexa methasone treatment (10 nM). SP-B immunofluorescence was very low in preculture specimens, increased duri ng culture, and was uniformly intense in epithelial cells of dexam ethasone-treated tissue. With a newly developed immunoassay, SP-B protein was undetectable in preculture lung «2% of adult), appeared during culture (26 % of adul t), and was furth er increased~3-fo ld by dexamethasone treatment (86 % of adult); lung tissu e of two newborn infants contained 7-9-fold more SP-B than is found in the adult. Using Western blot with enhanced chemiluminescence, mature SP-B was undetectable in 16-wk specimens but was Pulmonary surfactant isolated from bronchoalveolar lavage fluid contains a variety of lipids and proteins. Three SP have been identified that influence surfactant structure, function, or metabolism. SP-A is a hydrophili c protein of 28 -36-kD monomer size that has a numb er of demonstrated effects on surfactant in vitro both alone and interacting with other surfactant proteins. SP-B and SP-C are lipophilic proteins of approx imately 8 and 4 kD, respectively, that co-isolate with surfactant lipids. Both of these proteins enhance the rate of phospholipid film formation and improve the surface activity of lipid mixtures in vivo (rev iewed in Ref. 1).SP-B appears to be critically important for surfactant function in vivo. Antib odies to SP-B inactivate a replacement surfactant prepared from pig lungs and cause severe respiratory Received November 17, 1994; accepted May 9, 1995 present in 19-24-wk preculture tissue at 0.2-2.9% of the adult level. By comparison, SP-B mRNA content is 14 and 50 % of adult leve l in 19-and 24-wk lung tissue, respec tively; levels increase 3-fold during culture and a further 3-fold with dexamethason e. Based on these observed differences between mRNA and protein content, we conclude that basal SP-B gene exp ression in epithe lial ce lls of hum an fetal lung is regulated primarily at the level of translatio n or prote in stabil ity, where as glucocorticoids act transc riptionally. We specu late that SP-B protein acc umulates only as type II cells differentiate and acquire lamellar bodies for processing and storage of SP-B. (Pediatr R es 38: 668-675, 1995) Abbreviations SP , surfactant protein TBS, Tris-buffered salin e distress when instilled into the trachea of newborn animals or inoculated intraperitoneally into adult mice (2-4). In pulmonary function studies with preterm rabbits, Rider et al. (5) found that the activity of lipid-SP-B preparations was equivalent to that of natural surfactan t. Recently, Nog...

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“…Since SP-B is produced only in these well differentiated cell types, the gene of SP-B might be down-regulated in tumorigenic cells originating from these cell types. Hormones such as glucocorticoid have positive effects on SP-B synthesis (24). if this protein is involved in cellular differentiation and growth inhibitory mechanisms, hormonal treatment of Clara cell or type II pneumocyte derived NSCLCS may be promising.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes differentially expressed in normal lung and non-small cell lung carcinoma tissue

Schraml

Shipman²,

Colombi³

et al. 1995

Lung Cancer

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Using a magnet-assisted subtraction technique, 17 complementary DNA (eDNA) clones were isOlatedthat were expressed in the normal lung but were decreased or lost In the corresponding tumor tissue of a non small cell lung carcinoma patlent@The luck of expression of six magnet assisted subtraction technique eDNA clones in three additional non-small cell lung cardnoma cases indicates their possible relevance for non-small cell lung carcinoma. Two eDNA clones revealed homology to genes ape cifically expressed in lung, @e., pulmonary surfactant-associated protein B and the receptor for advanced glycosylation end products of proteins. Three cDNA clones showed identity to eDNA sequences encoding cal modulin-like protein, glutamine synthetase, and cytoskeletal 13-actln.One cDNA clone is identical to a recently described human expressed sequence tag whose gene is still unknown.

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Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung.

Cited by 165 publications

References 35 publications

Transcriptomic Analysis of Human Lung Development

Transcriptomic Analysis of Human Lung Development

Surfactant Protein B in Human Fetal Lung: Developmental and Glucocorticoid Regulation

Identification of genes differentially expressed in normal lung and non-small cell lung carcinoma tissue

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