Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lung development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1984

The effects of intermittent starvation on lung development in suckling rats.

The effect of starvation on postnatal lung growth in rats was investigated. Litters were starved twice, each time for 24 hours, on Day 1 and Day 5 after birth. One group of littermates was sacrificed on Day 7, and another group, on Day 14 of postnatal life. Intermittent starvation diminished lung growth. This was accompanied by reduced somatic growth. On postnatal Day 7, lung volume, total number of alveoli, and internal surface area of the lung were decreased in starved rats, but structurally their lungs appeared similar to control lungs. On postnatal Day 14, a striking morphologic difference was observed between the lungs of control and starved pups. Following starvation, retardation of lung growth was manifested in all the parameters studied. One week of normal uninterrupted suckling could not overcome the starvation-induced initial effects on growing lungs. It is concluded that starvation, soon after birth, affects adversely the normal development of lung.

Animal Population Groups↗
PubMed2002

Expression of cathepsins B, H, K, L, and S during human fetal lung development.

Cathepsins are involved in lysosomal protein degradation, proenzyme activation, antigen processing, and hormone maturation. They are secreted by tumor cells and macrophages and catalyze the remodeling of extracellular matrix proteins. To gain insight into the expression pattern of cathepsins during fetal lung development, the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were evaluated by using immunohistochemistry and in situ hybridization. Early expression of cathepsins B, H, and K was found in epithelial cells of the branching presumptive bronchi (<12th week of gestation). The most intense cathepsin K-specific immunoreactivity was found in developing airways with a lumen. Cathepsin K was found in epithelial cells only, whereas in contrast, cathepsins B and H were detected both in epithelial and interstitial cells. During fetal maturation, interstitial cells displayed cathepsin L immunoreactivity and, in the saccular phase (>26th week of gestation), both cathepsin L and S immunoreactivities. A continuous decline in the proportion of cathepsin H-positive interstitial CD68-positive cells was observed. These discrete temporal and spatial variations in cathepsin expression during organogenesis of the human lung indicate different physiological roles for the individual enzymes in different cell types and developmental stages.

Antigens, CD↗
PubMed1999

Nitric oxide synthase isoform expression in the developing lung epithelium.

Nitric oxide (NO), generated by NO synthase (NOS), is an important mediator of physiological processes in the airway and lung parenchyma, and there is evidence that the pulmonary expression of the endothelial isoform of NOS (eNOS) is developmentally regulated. The purpose of the present study was to delineate the cellular distribution of expression of eNOS in the developing respiratory epithelium and to compare it with inducible (iNOS) and neuronal (nNOS) NOS. Immunohistochemistry was performed on fetal (125-135 days gestation, term 144 days), newborn (2-4 wk), and maternal sheep lungs. In fetal lung, eNOS expression was evident in bronchial and proximal bronchiolar epithelia but was absent in terminal and respiratory bronchioles and alveolar epithelium. Similar to eNOS, iNOS was detected in bronchial and proximal bronchiolar epithelia but not in alveolar epithelium. However, iNOS was also detected in terminal and respiratory bronchioles. nNOS was found in epithelium at all levels including the alveolar wall. iNOS and nNOS were also detected in airway and vascular smooth muscle. The cellular distribution of all three isoforms was similar in fetal, newborn, and adult lungs. Findings in the epithelium were confirmed by isoform-specific reverse transcription-polymerase chain reaction assays and NADPH diaphorase histochemistry. Thus the three NOS isoforms are commonly expressed in proximal lung epithelium and are differentially expressed in distal lung epithelium. All three isoforms may be important sources of epithelium-derived NO throughout lung development.

Animals↗
PubMed2000

Immunohistochemical evidence for the occurrence of similar epithelial phenotypes during lung development and radiation-induced fibrogenesis.

PURPOSE: Processes of fibrosis, wound healing and tissue regeneration have in common the fact that proliferation and differentiation of cells involved in the restoration of normal-tissue architecture resemble to a certain degree the embryonic development of the corresponding tissue. The present review focuses on the phenotypic changes of alveolar epithelial cells during fibrogenesis and describes similarities in the expression pattern of epithelial antigens during lung development. METHODS: For comparative studies, immunohistochemical investigations of different experimental fibrosis models were performed. RESULTS: For several epithelial proteins, such as the CD44 adhesion molecule, the enzymes carbanhydrase II and cathepsin D, as well as the lectin galectin-3, a transient epithelial immunoreactivity have been detected. What all four examples have in common is that a part of the foetal antigenic profile reappears under conditions of injury and during the development of pulmonary fibrosis. CONCLUSIONS: The re-expression of foetal antigens in fibrotic samples with a spatio-temporal pattern, as detected by immunocytochemical techniques, indicates that some mechanisms or factors exist, which similarly regulate the differentiation of the epithelium during ontogenesis and in the remodelling process during fibrogenesis.

Animals↗
PubMed1997

Protein cross-linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development.

At birth, the mammalian lung is still immature. The alveoli are not yet formed and the interairspace walls contain two capillary layers which are separated by an interstitial core. After alveolarization (first 2 postnatal weeks in rats) the alveolar septa mature: their capillary layers merge, the amount of connective tissue decreases, and the mature lung parenchyma is formed (second and third week). During the first 3 wk of life the role of tissue transglutaminase (tTG) was studied in rat lung by immunostaining of cryostat and paraffin sections, by Northern and Western blotting, and by a quantitative determination of gamma-glutamyl-epsilon-lysine. While enzyme activity and intracellular tTG were already present before term, the enzyme product (gamma-glutamyl-epsilon-lysine-crosslink) and extracellular tTG appeared between postnatal days 10 and 19 in the lung parenchyma. In large blood vessels and large airways, which mature earlier than the parenchyma, both the enzyme product and extracellular tTG had already appeared at the end of the first postnatal week. We conclude that tTG is expressed and externalized into the extracellular matrix of lung shortly before maturation of an organ area. Because tTG covalently and irreversibly crosslinks extracellular matrix proteins, we hypothesize that it may prevent or delay further remodeling of basement membranes and may stabilize other extracellular components, such as microfibrils.

Animals↗
PubMed2002

The expression of PDGF, its receptors and capillary morphometry in the developing lung: quantitative studies.

The aim of the present study was the evaluation of the expression levels of PDGF-A and B, and PDGFR-alpha, andchanges of capillary cross-sectional areas during terminal vascular network formation in the developing lung. Pathogen-free fetuses and newborns used for rats were used. Lungs were processed for frozen section immunohistochemical staining and parallel tissue specimens were prepared for transmission electron microscopy. The expression levels of PDGF-A and B, and PDGFR-alpha were obtained using quantitative image analysis. Additionally. the morphometry of capillary cross-sectional area was performed. We found that the expression levels of the studied antigens fluctuated, and the highest values were found in21-day old fetuses (p < 0.0001). Although there were no significant differences of the area of "a single" capillary, the area of the endothelium decreased significantly in perinatal period (p <0.0001). We conclude that the statistically significant changes of the studied antigens' expression as well as the of capillary cross-sectional area occur in the perinatal period,

Animals↗
PubMed1995

Distinct expression patterns of CD44 isoforms during human lung development and in pulmonary fibrosis.

The transmembrane glycoprotein CD44 represents a family of molecules, all encoded by one gene. The variability of the isoforms is generated by alternative splicing of the nuclear RNA. Apart from the abundant standard form (CD44s), the variant isoforms (CD44v) are mostly restricted to epithelia. The present study demonstrates the expression of CD44s and CD44v isoforms in embryonic and fetal lungs and in normal and pathologically altered (pulmonary fibrosis after radio- or chemotherapy) human adult pulmonary tissues. Using double immunofluorescence and avidin biotin complex (ABC) techniques on paraffin sections, presence of CD44s and CD44v isoforms (CD44v4, CD44v6, CD44v9) has been analyzed. In normal lung tissue, CD44s is present at the cell surface of alveolar macrophages, in some interstitial cells and in epithelial cells. It is also present in epithelial and non-epithelial cells during lung development. CD44v isoforms containing exon v6 and v9 encoded epitopes are selectively detectable in normal epithelial cells with a strong basolateral distribution pattern in the entire population of type II pneumocytes and in basal cells of the bronchial epithelium. During development exon v9 encoded isoforms appear at the pseudoglandular stage, whereas CD44v6 has only been found at the saccular stage. Examination of 12 fibrotic lung samples has revealed major alterations in the CD44 expression in comparison to normal lung tissue. These changes include cytoplasmic deposits of CD44s in alveolar epithelial cells and reduced expression of the CD44v6 and CD44v9 isoforms in alveolar epithelial and bronchial epithelial cells. The results suggest that CD44v isoforms may be utilized by type II pneumocytes in epithelial-mesenchymal interactions and in the maintenance of the pulmonary histoarchitecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Expression of ABCA3 in developing lung and other tissues.

ABCA3 is a member of the ATP-binding cassette (ABC) family of transport proteins and is required for perinatal respiratory adaptation. Monoclonal and polyclonal antibodies were generated against a recombinant human ABCA3 peptide and used to assess its expression in the developing lung and adult tissues. Immunostaining for ABCA3 was detected at highest levels in type II epithelial cells of the lung but was also noted in other organs including liver, stomach, kidney, adrenal, pancreas, trachea, and brain. In the fetal lung, ABCA3 staining and mRNA increased prior to birth. Like other surfactant protein genes, ABCA3 expression was induced by thyroid transcription factor-1 in vitro. ABCA3 was coexpressed with SP-B and proSP-C in type II epithelial cells. ABCA3 staining was detected surrounding large, intracellular organelles consistent with its association with lamellar bodies. In the human fetal lung, ABCA3 staining was not detected prior to 22-23 weeks of gestation, except in the presence of pulmonary inflammation. ABCA3 was detected in type II epithelial cells of the human lung from 28 weeks of gestation and thereafter. Postnatally, intense ABCA3 staining was observed in hyperplastic epithelial cells relining injured airways in infants with chronic lung disease. Localization and regulation of ABCA3 in the respiratory epithelium is consistent with its proposed role in surfactant homeostasis. The role of ABCA3 in extrapulmonary tissues and organs remains to be elucidated. This manuscript contains online supplemental material at (www.jhc.org). Please visit this article online to view these materials.

ATP-Binding Cassette Transporters↗
PubMed1999

Proliferation and differentiation defects during lung development in corticotropin-releasing hormone-deficient mice.

Corticotropin-releasing hormone-deficient (CRH-KO) mice, which as a consequence are also glucocorticoid-insufficient, exhibit neonatal lethality when derived from CRH-KO mothers. Death is due to respiratory insufficiency as a result of abnormal pulmonary development, and can be prevented by prenatal administration of glucocorticoids. In the study described here, we used CRH-KO mice as a model of genetically altered in utero glucocorticoid action to elucidate the role of endogenous glucocorticoids in lung maturation. The histologic appearance of the lungs of these mice is normal until Day 17.5 of gestation, at which point failure of septal thinning and air-space formation is observed. These morphologic alterations in the CRH-KO mouse lung are the result of continued cell division in cellular compartments that by this time in gestation have ceased proliferating in wild-type mice, rather than the result of a failure of apoptosis. In accord with this observation, the CRH-KO lung exhibits delayed induction of type II pneumocyte biochemical parameters, such as messenger RNAs (mRNAs) for surfactant protein-A (SP-A) and SP-B, and fatty acid synthase, as well as delayed Clara cell maturation. In contrast, surfactant phospholipid synthesis is not impaired during CRH-KO lung development. Our findings indicate that an essential role of endogenous glucocorticoids in pulmonary maturation in utero is to stimulate a developmental program in late gestation that affects epithelial and mesenchymal cell proliferation and differentiation throughout the parenchyma.

Animals↗
PubMed1990

Laminin in lung development: effects of anti-laminin antibody in murine lung morphogenesis.

The pattern of deposition and the role of laminin, a major glycoprotein constituent of basement membranes, were investigated during lung morphogenesis in the fetal mouse. Lung primordia were removed from Day 13 embryos, right lower lobes were further dissected and placed in filter membrane assemblies. Explants were then cultured at the liquid-air interface for 3 days in the presence of anti-laminin, anti-thrombospondin (another extracellular matrix constituent), preimmune serum, laminin-neutralized anti-laminin, or medium alone. Cultures were monitored by (direct) phase-contrast microscopy, light microscopy, and immunofluorescence. We found that anti-laminin antibodies altered normal lung morphogenesis in a dose-dependent manner. The anti-laminin-treated explants presented a marked inhibition of branching morphogenesis and a distortion of the bronchial tree. A lower rate of growth was also observed in the explants exposed to this antibody. High concentrations of anti-thrombospondin antibodies, normal rabbit serum, or laminin-neutralized anti-laminin antibodies had no effect on lung morphogenesis. These results were not modified by culturing the explants in submersion culture or on Vitrogen 100-coated surfaces.

Animals↗
PubMed2006

Altered postnatal lung development in C3H/HeJ mice.

C3H/HeJ mice develop an increase in terminal air space area detectable by postnatal d 14 that persists into adulthood compared with strain-matched controls (C3H/SnJ, C3H/OuJ). Morphometric quantification revealed a 50% increase in terminal air space area by postnatal d 14 and a 2.3-fold increase by 2 mo of age in C3H/HeJ mice. Bacteriologic cultures obtained from the left lung on postnatal d 7 revealed > 100 colony-forming units (CFU)/left lung of predominantly Gram-negative bacteria (GNB) (Escherichia coli and Proteus mirabilis) in 13 of the 14 C3H/HeJ mice compared with 0 of 12 controls demonstrating colonization of the developing lung in C3H/HeJ mice. An approximately threefold increase in macrophages from bronchoalveolar lavage, threefold increases in matrix metalloproteinase 12 (MMP-12) mRNA and protein levels and elevated levels of proinflammatory cytokines monocyte chemoattractant protein (MCP-1) and keratinocyte-derived cytokine (KC) were also found. P. mirabilis obtained from lung cultures in C3H/HeJ mice induced nuclear factor-kappaB (NF-kappaB) activation in human embryonic kidney 293 (HEK 293) cells transfected with TLR5. In C3H/HeJ mice lacking TLR4 signaling, bacterial colonization is associated with chronic inflammation and permanent changes in lung morphology.

Animals↗
PubMed1991

EGF and TGF alpha influence in vitro lung development by the induction of matrix-degrading metalloproteinases.

Remodeling of the extracellular matrix by matrix-degrading metalloproteinases (MMPs) has been implicated in the early morphogenesis of branched organs. Growth factors such as EGF and TGF alpha are known to regulate the expression of MMPs in a variety of systems. We therefore examined the effects of EGF, TGF alpha, and collagenase upon in vitro branching of the embryonic lung. Lung rudiments from 11.5 day post coitum mice underwent extensive growth and repetitive branching during a 3-day period in organ culture. Lungs treated with EGF or TGF alpha were larger than controls, yet displayed fewer branches along with markedly dilated end buds which lacked clefts, indicating that these growth factors inhibit normal lung branching. Addition of purified mammalian collagenase to lung cultures similarly inhibited epithelial branching and produced end bud enlargement. In addition, gelatin-substrate enzymography of the conditioned medium from EGF- and TGF alpha-treated lungs revealed a marked induction of a metalloproteinase activity which most likely corresponds to the 72kDa type IV collagenase/gelatinase which degrades basement membrane collagens. Lungs maintained in the presence of both TGF alpha and TIMP, a specific inhibitor of MMPs, branched repeatedly and displayed normal, narrow end buds as seen with controls, suggesting that TIMP is capable of preventing or reversing the observed growth factor mediated effects upon lung branching. Taken together, these results provide evidence that the growth factors EGF and TGF alpha guide lung development, at least in part, by inducing the expression of matrix-degrading metalloproteinases.

Animals↗
PubMed1997

Lung development and early origins of childhood respiratory illness.

In the last two decades, 5 cohort studies have been initiated to examine the association of infant respiratory function with genetic and environmental risk factors, as well as with subsequent lower respiratory illness in early childhood. While the current complexity of respiratory function tests in this age group precludes study samples with sufficient power to examine more complex issues, information from these studies has provided an exciting adjunct to that available from the longer cohort studies. Premorbid alterations in airway function or lung development increase the risk of wheezing lower respiratory illnesses during the preschool years and the risk of impaired airway function at 5-6 years of age. In addition, gender differences in airway function and the response to maternal smoking have been observed. Larger collaborative population-based studies are needed to explore the environmental, genetic and immunological mechanisms responsible, but will depend on the development of less invasive tests of airway function appropriate for use in healthy infants.

Adolescent↗
PubMed1999

Regulation of vasodilator synthesis during lung development.

The endothelium-derived vasodilator molecules prostaglandin I2 (PGI2) and nitric oxide (NO) are critically involved in the dramatic increase in pulmonary blood flow that occurs during cardiopulmonary transition at birth. Studies in animal and cell culture models have revealed that there is increased PGI2 and NO production in the pulmonary circulation of the late fetus in direct response to increased oxygenation, and that this response is unique to the pulmonary endothelium. Additional work has demonstrated that there is normally marked upregulation in the expression of the key synthetic enzymes cyclooxygenase type I and endothelial NO synthase in the lung during late gestation, thereby maximizing the capacity for vasodilator production at the time of birth. Furthermore, studies in animal models of neonatal pulmonary hypertension indicate that attenuated expression of these genes may frequently contribute to the pathogenesis of the disorder. A greater understanding of the mechanisms regulating PGI2 and NO synthesis in the developing lung will potentially lead to novel therapies for neonatal pulmonary hypertension aimed at optimizing endogenous vasodilator production.

Endothelium, Vascular↗
PubMed2001

Quantitative immunohistochemical analysis of the expression of CD31 during lung development in the rat.

The CD31 antigen, known also as the platelet/endothelial cell adhesion molecule 1, has been shown to be a good marker for monitoring the formation of the vasculature in mammals. Available evidence suggests that the expression of CD31 is regulated during embryonal and fetal development. The aim of the present study was to evaluate the changes in the expression of CD31 during the development of the rat lung. We studied samples of lung tissue from rat fetuses (17, 19 and 21 days after conception), newborns (1, 3, 5, 7, 14 and 21 days after birth) and adult animals. The tissue samples from rats in the various age groups were divided into sets, with all age groups being represented in every set. After immunohistochemical localization of the antigen, the amount of chromogen deposited after the immunoreaction (defined in terms of optical density; OD) was evaluated by image analysis in the various sets. Measurements were obtained twice from each set, and the results were reproducible (paired t test, alpha = 0.05). We subjected the results of measurements from all sets to an analysis of variance (ANOVA). The amount of chromogen (OD) decreased from fetal day 19 to 5 days after delivery and then increased again. The decrease in the level of expression of CD31 on days 3 and 5 after delivery was significant (p < 0.0001).

Animals↗