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PubMed2004

Inhaled nitric oxide attenuates pulmonary hypertension and improves lung growth in infant rats after neonatal treatment with a VEGF receptor inhibitor.

VEGF plays a critical role during lung development and is decreased in human infants with bronchopulmonary dysplasia. Inhibition of VEGF receptors in the newborn rat decreases vascular growth and alveolarization and causes pulmonary hypertension (PH). Nitric oxide (NO) is a downstream mediator of VEGF, but whether the effects of impaired VEGF signaling are due to decreased NO production is unknown. Therefore, we sought to determine whether impaired VEGF signaling downregulates endothelial NO synthase (eNOS) expression in the developing lung and whether inhaled NO (iNO) decreases PH and improves lung growth after VEGF inhibition. Newborn rats received a single dose of SU-5416 (a VEGF receptor inhibitor) or vehicle by subcutaneous injection and were killed up to 3 wk of age for assessments of right ventricular hypertrophy (RVH), radial alveolar counts (RAC), lung eNOS protein, and NOx production in isolated perfused lungs (IPL). Neonatal treatment with SU-5416 increased RVH in infant rats and reduced RAC. Compared with controls, SU-5416 reduced lung eNOS protein expression by 89% at 5 days (P < 0.01). IPL studies from day 14 rats demonstrated increased baseline pulmonary artery pressure and lower perfusate NOx concentration after SU-5416 treatment. Importantly, iNO treatment prevented the increase in RVH and improved RAC after SU-5416 treatment. We conclude that treatment of neonatal rats with SU-5416 downregulates lung eNOS expression and that iNO therapy decreases PH and improves lung growth after SU-5416 treatment. We speculate that decreased NO production contributes to PH and decreases distal lung growth caused by impaired VEGF signaling.

Administration, Inhalation↗
PubMed1988

Immunohistochemical localization of pulmonary surfactants in fetal rabbit lung.

Differentiation and proliferation of the alveolar epithelial cells in fetal rabbit lung were studied by using immunohistochemical techniques. To observe the differentiation of type II alveolar epithelial cells, an antibody to purified rabbit surfactant was prepared and its specificity was checked by Western blot analysis. This antibody reacted with the 29-35 kDa protein group, which was presumed to be the major surfactant associated protein group in rabbit. After immunohistochemical staining, surfactant stained type II cells first appeared during the canalicular stage of fetal lung development. And they were detected prominently in the proximal portion of primitive alveolar zones and the number of stained cells increased rapidly in the succeeding gestational days. Clara cells were also reacted with this antibody during the alveolar stage. The distribution of DNA-synthesizing cells in the developing lung indicated that proliferation of alveolar epithelial cells is reduced earlier in the proximal portion than in the distal portion of primitive alveolar zones. These results suggest that differentiation of type II cells begins during the canalicular stage and it begins earlier in the proximal portion of primitive alveolar zones, which has already ceased prominent proliferation.

Animals↗
PubMed1979

Structural aspects of gas exchange.

The lung is composed of several million small air spaces, lined by a delicate tissue membrane separating air from capillary blood. The design features of the gas exchange region in the lung are optimal for gaseous diffusion, by having a very extensive contact surface but with a minimal tissue barrier composed of an epithelial and endothelial layer separating an interstitial layer. The extent of the gas exchange surface in adult lungs is determined by general maturation which in turn is influenced by metabolic requirements of the organism. Environmental factors can modulate the pattern of ultimate lung development. Lung inflation causes air spaces to expand mainly by a process of tissue unfolding beneath an extremely thin layer of alveolar surfactant. This ensures cellular integrity during extreme deformations while at the same time providing a reserve of gas exchange surface so that functional diffusion capacity at all lung volumes is less than the structural maximum.

Animals↗
PubMed2000

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Chronic Disease↗
PubMed2004

Innervation of pulmonary neuroendocrine cells and neuroepithelial bodies in developing rabbit lung.

We investigated the development of innervation of the pulmonary neuroendocrine cell (PNEC) system composed of single cells and organoid cell clusters, neuroepithelial bodies (NEB) in rabbit fetal and neonatal lungs. To visualize the nerve fibers and their contacts with PNECs/NEBs, we used confocal microscopy and multilabel immunohistochemistry (IHC) with pan-neural marker, synaptic vesicle protein 2 (SV2), and serotonin (5-HT) as markers for PNECs/NEBs, and smooth muscle actin or cytokeratin to identify airway landmarks. The numbers and distribution of PNEC/NEB at different stages of lung development (E16, 18, 21, 26, and P2) and the density of innervation were quantified. First PNECs immunoreactive for 5-HT were identified in primitive airway epithelium at E18 as single cells or as small cell clusters with or without early nerve contacts. At E21 a significant increase in the number of PNECs with formation of early innervated NEB corpuscules was observed. The overall numbers of PNECs/NEBs and the density of mucosal, submucosal, and intercorpuscular innervation increased with progressing gestation and peaked postnatally (P2). At term, the majority of NEBs and single PNECs within airway mucosa possessed neural contacts. Such an extensive and complex innervation of the PNEC system indicates a multifunctional role in developing lung and during neonatal adaptation.

Animals↗
PubMed2007

Expression profiling and lung cancer development.

Recent lung cancer research has been directed to using molecular approaches to facilitate early diagnosis, to identify clinically relevant biological factors associated with histologic heterogeneity, and to identify novel therapeutic agents. This research takes advantage of technical advances that allow rapid high throughput assays to interrogate the genome, proteome, and epigenome. In this review of gene expression profiling in lung carcinogenesis, we will focus upon recent advances in the understanding of malignant transformation of lung epithelial cells and of lung cancer differentiation and progression. These studies have provided important information about the genomic alterations of tobacco smoke-associated airway field carcinogenesis and about the developmental pathways that mediate lung tumor invasion and histologic differentiation in response to injury.

Adenocarcinoma↗
PubMed1981

Modulation of tropoelastin production and elastin messenger ribonucleic acid activity in developing sheep lung.

During fetal development of the sheep lung, elastin content continually increases. For examination of the processes controlling this elastin accumulation, an explant culture system was characterized with respect to changes in tropoelastin production in sheep lung during fetal and early postnatal development. Relative tropoelastin production in cultured lung explants, quantitated by immunoprecipitation, was about 0.3% of total [14C] valine incorporation during the period from 55 to 104 days after conception. This percentage began to increase by 112 days after conception, reached a maximum value of about 1.0% by 135 days after conception, and then declined to 0.5% soon after birth. The absolute rate of tropoelastin production paralleled these changes in relative tropoelastin production. For evaluation of the processes controlling tropoelastin production in the developing sheep lung, total cellular RNA prepared from 68-day-old fetal, 107-day-old fetal, and 147-day-old fetal lung was translated in a rabbit reticulocyte lysate system. Elastin mRNA activity, expressed as the amount of elastin precursor translated per microgram per microgram of DNA, increased about 3-fold during fetal lung development, and elastin precursor synthesis, expressed as a proportion of total translational activity, increased in parallel. It appears, therefore, that elastin production in developing fetal lung is modulated, at least in part, by the amount of available translatable elastin mRNA present in the tissue.

Animals↗
PubMed2000

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, Issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: We identified eight studies which met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g. , washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Aerosols↗
PubMed1997

Early fetal development of lung vasculature.

Despite its relevance to a variety of congenital anomalies, the earliest stages of lung vascular development are poorly understood. In other organs, two processes have been identified: vasculogenesis, the development of blood lakes in mesenchyme, and angiogenesis, the branching of new vessels from preexisting ones. In the present study we established the events in the development of the lung's vasculature in Swiss-Weber mouse fetuses between 9 and 20 days gestation, using light microscopy (LM), transmission electron microscopy (TEM), barium-gelatin angiograms, and scanning electron microscopy (SEM) of Mercox (methyl methacrylate) vascular casts. Three features were identified: (1) central sprouting or angiogenesis for up to approximately seven generations (counting the artery to each lung as first generation); (2) the formation of peripheral lakes by vasculogenesis; and (3) the development of communications between the central and peripheral systems. At 9 days gestation, intercellular spaces were apparent in the lung mesenchyme; these were formed by discharge of vesicles from mesenchymal cells, which then regrouped to provide "endothelial" cells lining the spaces. The isolated lakes coalesced to form sinusoidal spaces of irregular profile. At 12 days gestation, the earliest time at which were able to make a cast, sprouting of arteries and veins from the central pulmonary vascular trunks was apparent. Between 13 and 14 days gestation the earliest connection between the peripheral and central spaces was identified. Such connections became more numerous and dense by term. Similar images seen on examination of human fetal lung sections by LM indicated that similar processes occur in the vascular development of the human lung.

Animals↗
PubMed1984

Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque.

To test the effect of dose and time on fetal lung maturation by exogenous glucocorticosteroids, triamcinolone acetonide was given to time-mated pregnant rhesus macaques (Macaca mulatta). Triamcinolone acetonide (10 mg/kg or 1 mg/kg) was administered intramuscularly during the midpseudoglandular (63 to 65 days' gestational age) or midcanalicular phase (110 to 112 days' gestational age) of lung development. Fetectomies were performed at 90, 120, or 150 days' gestational age. Nontreated control fetuses and postnatal animals from 59 days' gestational age to 31 days' postnatal age were collected for study of normal developmental lung morphology in the rhesus monkey. Lungs from fetuses of 90 days' gestational age and older were fixed by tracheal infusion, and lungs from fetuses less than 90 days' gestational age were fixed by immersion and embedded for high-resolution light microscopy. Body weight, crown-rump length, and fixed lung volume were determined for all fetuses. Morphometric evaluation of the volume percent of parenchyma, the volume percent of air space and the mean linear intercept as an estimate of air space size was also done. Lungs from fetuses treated during the canalicular phase had thinner, longer, less cellular septa, larger air spaces, and increased numbers of alveolar divisions in terminal air spaces as compared to those of controls. Lungs of fetuses treated during the pseudoglandular phase also had some septa which were thinner, less cellular, and longer than those of controls and had a marked increase in air space size. However, most septa were greatly reduced in height and appeared fewer in number. Alveolar divisions were decreased. The volume percent of air space was larger in all treated groups. Fixed lung volume normalized to body size (body weight and crown-rump length) was greater than that for controls for the high-dose canalicular phase treatment group. The same parameter was lower than that of controls for the high-dose, pseudoglandular phase treatment group of 150 days' gestational age. Body weight and crown-rump length for all pseudoglandular phase triamcinolone acetonide-treated fetuses also tended to be lower than those of controls. We concluded that: (1) there is both a time-dependent and a dose-dependent effect on triamcinolone acetonide on fetal lung maturation in rhesus macaques, (2) triamcinolone acetonide accelerates maturation of the interstitial and epithelial component of the developing fetal rhesus lung independent of age, (3) triamcinolone acetonide accelerates alveolarization only at later treatment ages, and (4) triamcinolone acetonide induces retardation of growth of some of the lung septa and body growth only

Animals↗
PubMed1984

Butylated hydroxyanisole and lung tumor development in A/J mice.

A diet containing 0.75% butylated hydroxyanisole (BHA) did not enhance the development of lung tumors in A/J mice if fed for 8 weeks after administration of urethan, benzo[a]pyrene (B[a]P), or dimethylnitrosamine (DMN). Prefeeding animals with BHA partially protected animals against the tumorigenic effect of urethan and B[a]P. Partial protection was also seen in animals given B[a]P and then exposed to BHA in the diet. The two isomers of BHA (3-tert.-butyl-4-hydroxyanisole and 2-tert.-butyl-4-hydroxyanisole) were synthesized and injected ip. They failed to enhance lung tumor development. It is concluded that BHA is not a promoting agent as is butylated hydroxytoluene (BHT) for lung tumors in mice. One possible explanation is that BHA in the diet does not produce the extensive cell proliferation seen in the lungs of mice fed BHT.

Animals↗
PubMedDate not supplied

[Evaluation of radon effects on lung cancer development].

In order to evaluate the effect of indoor exposure to radon and thoron on the development of lung cancer in the population of two towns of Sverdlovsk Region, epidemiologic studies were conducted using a multifactarial method of analysis. Both towns, Pervouralsk and Karpinsk, are located within the geological area with the gamma-radiation exposure dose ranging from 5 to 12 mu r/hr, and are characterized by an increased cancer incidence rate--323.1 and 364.6 cases per 100,000 of population, respectively. The mean values of the voluminous indoor activity (VA) of radon in Pervouralsk and Karpinsk were 23 and 75 Bq/m3 (with maximal indices of radon VA being 395 and 739 Bq/m3), equivalent equilibrium concentrations (EEC) of residential radon and thoron were 0.6 and 2.5 Bq/m3 (maximal indices of EEC of thoron being 5 and 13 Bq/m3), respectively. The results of multifactorial analysis of 22 different lung cancer risk factors carried out using the pattern recognition method proved that the contribution of thoron and radon in the development of lung cancer in the population of Pervouralsk and Karpinsk was not significant--0.5 and 0.6%, respectively. The calculations performed in a monofactorial model of risk evaluation BEIR VI gave different results--11-16% and 35-52% for the towns of Pervouralsk and Karpinsk, respectively. The discussion of the results provides arguments for the reliability and adequacy of the application of multifactorial method of radiation risk evaluation as compared to the traditionally applied monofactorial method.

Air Pollution, Indoor↗
PubMed1988

Postnatal development of rat lung following retarded fetal lung growth.

Postnatal lung development was examined in rats born with smaller than normal lungs after either prenatal exposure to glucocorticoid or to an inhibitor of collagen synthesis. At birth, treated animals had lower than normal lung weights, lung to body weight ratios, hydroxyproline (HYP) levels, total DNA; and rates of DNA synthesis. Rats exposed to steroid showed a rapid recovery in growth during the normal postnatal cell proliferative phase from 4 to 11 days, though collagen levels did not return to normal until 3 weeks of age. Rats exposed to a prenatal proline analog showed a much slower rise in lung weight and total DNA, and these levels were still much below normal at 2-3 weeks when the cell proliferation phase was completed. Levels of disaturated phosphatidylcholine were significantly below normal up to 11 days, whereas total HYP was significantly reduced and less fibrillar collagen was seen in the lung throughout the study. The results indicate that the smaller but mature lungs at birth after antenatal steroid show a growth rebound and quickly become structurally normal. In contrast, inhibition of fibroblast growth and collagen deposition produces small lungs at birth, which continue to show inhibited growth and development at least up to 3 weeks of age, when the cell division phase is over.

Animals↗
PubMed2006

Interaction of epithelium with mesenchyme affects global features of lung architecture: a computer model of development.

Lung airway morphogenesis is simulated in a simplified diffusing environment that simulates the mesenchyme to explore the role of morphogens in airway architecture development. Simple rules govern local branching morphogenesis. Morphogen gradients are modeled by four pairs of sources and their diffusion through the mesenchyme. Sensitivity to lobar architecture and mesenchymal morphogen are explored. Even if the model accurately represents observed patterns of local development, it could not produce realistic global patterns of lung architecture if interaction with its environment was not taken into account, implying that reciprocal interaction between airway growth and morphogens in the mesenchyme plays a critical role in producing realistic global features of lung architecture.

Bronchi↗
PubMed2004

PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung.

We examined the roles of the PI3K-AKT signalling pathway in fetal lung development. By Western blotting, phosphorylated AKT (pAKT) was highly expressed in fetal days 12 and 14 with decreased expression thereafter. By immunohistochemistry, pAKT was expressed mainly in the respiratory epithelium of early fetal days. We examined the effects of fibroblast growth factor 1 (FGF1), PI3K inhibitors (LY294002 and wortmannin), MAPK inhibitor (PD98059) and both of FGF1 and each inhibitor on lung morphogenesis, BrdU incorporation and apoptosis. In the FGF1-treated explants, the number of terminal buds and BrdU-labelled cells increased significantly, while the LY294002-, wortmannin-, PD98059-treated explants demonstrated obvious decreases. The effects by FGF1 were inhibited by LY294002, wortmannin and PD98059. Regardless of the presence of FGF1, the LY294002-, wortmannin- and PD98059-treated explants increased apoptosis revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay in the mesenchyme of the explants. At the same time, the effect of LY294002, wortmannin, PD98059 on expression of surfactant apoprotein C (SPC) were also studied. The LY294002 and wortmannin treatments showed decreased expression of SPC. These findings suggest that the PI3K-AKT signalling pathway plays a pivotal role in mouse lung development through various biological processes.

Androstadienes↗
PubMed1999

Bombesin inhibits apoptosis in developing fetal rat lung.

We have shown recently that apoptosis occurs during fetal and postnatal lung development. Our hypothesis that branching morphogenesis occurs through a delicate balance of cell proliferation and apoptosis predicts that substances that enhance branching of the airways would affect both cell proliferation and apoptosis in the lung. Bombesin-like peptides have a mitogenic effect on bronchial epithelium and fibroblasts, and bombesin has been shown to enhance branching morphogenesis in fetal lung. We used organ cultures of 16-day gestation fetal rat lung to study the effects of bombesin on apoptosis. Cultures were incubated in serumless medium alone or exposed to 1microM bombesin for 0-48 h. Levels of apoptosis were quantified using the TUNEL assay and expressed as percentage of apoptotic cells in paraffin sections of explants. Bombesin significantly inhibited apoptosis in fetal lung mesenchyme 48 h in culture by more than 50% (p < 0.05). The effects of bombesin on apoptosis were prevented completely if explants were exposed to the specific bombesin receptor antagonist, [D-Phe12]bombesin. To examine if the absence of serum in the media could have accounted for some of these effects, explants were cultured for 48 h in serumless medium, medium containing 10% fetal bovine serum, serumless medium with 1 microM bombesin, or medium containing both 10% fetal bovine serum and 1 microM bombesin. The addition of fetal bovine serum to the media reduced apoptosis significantly. The effect of fetal bovine serum on apoptosis was additive with bombesin. We conclude that bombesin inhibits apoptosis in developing fetal rat lung mesenchyme through its interaction with the bombesin receptor.

Animals↗
PubMed2005

Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5.

Wnt7b is a Wnt ligand that has been demonstrated to play critical roles in several developmental processes, including lung airway and vascular development and chorion-allantois fusion during placental development. Wnt signaling involves the binding of Wnt ligands to cell surface receptors of the frizzled family and coreceptors of the LRP5/6 family. However, little is known of the ligand-receptor specificity exhibited by different Wnts, Fzds, and LRPs in Wnt signaling. Expression analysis of Fzds and LRP5/6 in the developing lung and vasculature showed that Fzd1, -4, -7, and -10 and LRP5/6 are expressed in tissue-specific patterns during lung development. Fzd1, -4, and -7 are expressed primarily in the developing lung mesenchyme, and Fzd10 is expressed in airway epithelium. LRP5 and LRP6 are expressed in airway epithelium during lung development, whereas LRP5 but not LRP6 expression is observed in the muscular component of large blood vessels, including the aorta. Cell transfection studies demonstrate that Wnt7b can activate the canonical Wnt pathway but not the noncanonical Wnt pathway in a cell-specific manner. Biochemical analysis demonstrates that Wnt7b can bind to Fzd1 and -10 on the cell surface and cooperatively activate canonical Wnt signaling with these receptors in the presence of LRP5. Together, these data demonstrate that Wnt7b signals through Fzd1 and -10 and LRP5 and implicate these Wnt coreceptors in the regulation of lung airway and vascular development.

Animals↗
PubMed1991

Longitudinal study of lung function development in a cohort of Indian medical students: interaction of respiratory allergy and smoking.

This study was done to identify some factors that affect the growth and development of lung function during adolescence and early adulthood. Forced expiratory spirograms and peak expiratory flow rates were obtained in a cohort of normal young men (n = 63) over a period of 4 years, at intervals of approximately 2 years. Two factors that disturbed the normal pattern of lung function development in this group were smoking and respiratory allergy. Among the smokers and the allergics the decline in the forced expiratory volume expressed as a percentage of the forced vital capacity (FEV1%), the forced expiratory flow in the middle half of the forced vital capacity (FEF25-75%) and the FEF25-75% expressed as a ratio of the forced vital capacity (FEF/FVC) was more than double that among the normal subjects. The number of smokers and of allergics increased during the course of the study from 15 to 19 and from 16 to 23 respectively. There was a significant (P less than .01) interaction between smoking and the manifestation of respiratory allergy. Among nonsmokers, the number of allergic subjects increased from 12 to 13, while among smokers it increased from 4 to 10, during the four years.

Adolescent↗