Insulin regulation of messenger ribonucleic acid for the surfactant- associated proteins in human fetal lung in vitro

Dekowski, Steven A.

doi:10.1210/en.131.2.669

Cited by 32 publications

(31 citation statements)

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“…In fetal rat lung explants, no consistent alteration in SP-A mRNA content was observed at different glucose concentrations (24). Insulin at pharmacological doses inhibited surfactant protein A gene expression in vitro (25,26).…”

Section: Ferná Ndez-real and Associatesmentioning

confidence: 93%

Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

et al. 2008

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OBJECTIVES -Impaired lung function and inflammation have both attracted interest as potentially novel risk factors for glucose intolerance, insulin resistance, and type 2 diabetes. We hypothesized that circulating levels of surfactant protein (SP)-A, which reflects interstitial lung injury, could be associated with altered glucose tolerance and insulin resistance.RESEARCH DESIGN AND METHODS -Circulating SP-A concentration and metabolic variables (including insulin sensitivity by minimal model method, n ϭ 89) were measured in 164 nonsmoking men.RESULTS -Circulating SP-A concentration was significantly higher among patients with glucose intolerance and type 2 diabetes than in subjects with normal glucose tolerance, even after adjustment for BMI, age, and smoking status (ex/never). The most significant differences were found in overweight and obese subjects with altered glucose tolerance (n ϭ 59) who showed significantly increased serum SP-A concentrations (by a mean of 24%) compared with obese subjects with normal glucose tolerance (n ϭ 58) (log SP-A 1.54 Ϯ 0.13 vs. 1.44 Ϯ 0.13; P Ͻ 0.0001). Insulin sensitivity (P ϭ 0.003) contributed independently to 22% of SP-A variance among all subjects. In subjects with altered glucose tolerance, insulin sensitivity (P ϭ 0.01) and fasting triglycerides (P ϭ 0.02) contributed to 37% of SP-A variance. Controlling for serum creatinine or C-reactive protein in these models did not significantly change the results.CONCLUSIONS -Lung-derived SP-A protein was associated with altered glucose tolerance and insulin resistance in 164 nonsmoking men. Diabetes Care 31:958-963, 2008

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Section: Ferná Ndez-real and Associatesmentioning

confidence: 93%

Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

et al. 2008

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“…Total RNA was isolated from whole lung tissue obtained at 0, 6, 10, 12, and 16 d postnatal age using RNAzol as described previously (18). Ribonuclease protection analysis was used to quantify the steady-state levels of the platelet-derived growth factor receptor ␣ (PDGF-R␣) mRNA in lung tissue from wild-type and RAR␤ null mice at various postnatal ages.…”

Section: Alveolarization In Rar␤ Null Micementioning

confidence: 99%

Alveolarization in Retinoic Acid Receptor-β–Deficient Mice

et al. 2005

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Retinoids bind to nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. RAR␤, one of three isoforms of RARs (␣, ␤, and ␥), is expressed in the fetal and adult lung. We hypothesized that RAR␤ plays a role in alveolarization. Using morphometric analysis, we determined that there was a significant increase in the volume density of airspace in the alveolar region of the lung at 28, 42, and 56 d postnatal age in RAR␤ null mice when compared with wild-type controls. The mean cord length of the respiratory airspaces was increased in RAR␤ null animals at 42 d postnatal age. Respiratory gasexchange surface area per unit lung volume was significantly decreased in RAR␤ null animals at 28, 42, and 56 d postnatal age. In addition, alveolar ducts tended to comprise a greater proportion of the lung airspaces in the RAR␤ null mice. The RAR␤ null mice also had impaired respiratory function when compared with wild-type control mice. There was no effect of RAR␤ gene deletion on lung platelet-derived growth factor (PDGF) receptor ␣ mRNA levels in postnatal lung tissue at several postnatal ages. However PDGF-A protein levels were significantly lower in the RAR␤ null mice than in wild-type controls. Thus, deletion of the RAR␤ gene impairs the formation of the distal airspaces during the postnatal phase of lung maturation in mice via a pathway that may involve PDGF-A. Retinoids regulate the development of the conducting airways and the gas-exchange portion of the lung (1). The major biologically active retinoid, all-trans retinoic acid, is a metabolite of retinol (vitamin A) (2). Retinol can be stored within lung tissue esterified to fatty acids, where it can be released by retinyl ester hydrolases and then be converted to all-trans retinoic acid (1). All-trans retinoic acid binds with high affinity to retinoic acid receptors (RARs), which exist in three isoforms, ␣, ␤, and ␥ (3). Retinoid X receptors (RXRs) primarily bind 9-cis retinoic acid (3). RARs form a heterodimer with RXRs and bind to retinoid responsive elements in target genes (3). RARs and RXRs are members of the steroid hormone receptor superfamily of transcription factors (3).Massaro and co-workers (4,5) reported that all-trans retinoic acid increases the number of alveoli in rat lung. In the first study, postnatal rats that were treated with all-trans retinoic acid had increased numbers of alveoli and increased gas exchange surface area (4). A synthetic glucocorticoid, dexamethasone, decreases the number of alveoli in this animal model. All-trans retinoic acid overcame the inhibitory effects of dexamethasone on alveolarization in the postnatal rats (4). In the second study, elastase was insufflated into the lungs of adult rats to create a model of emphysema, i.e. the damaged lungs in the treated rats were characterized by fewer and larger alveoli and decreased gas exchange area (5). When the elastase-treated rats received an injection of all-trans retinoic acid, the emphysema-like effects of the elastase treatment were almost completely reversed, i...

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“…The human fetal lung explant system has been used to study type II alveolar cell differentiation (16), the hormonal regulation of gene expression (17,23), the effects of GC on lung structure (17), as well as the metabolism of GC (24). We observed that HSD2 is expressed at discrete sites in the undifferentiated human fetal lung tissue.…”

Section: Discussionmentioning

confidence: 94%

11-β Hydroxysteroid Dehydrogenase Type 2 in Human Adult and Fetal Lung and Its Regulation by Sex Steroids

et al. 2007

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11-␤ hydroxysteroid dehydrogenase type 2 (HSD2) oxidizes the biologically active glucocorticoid (GC), cortisol, to inactive cortisone. We characterized HSD2 gene expression and activity in human adult and fetal lung tissues and in cultured fetal lung explants, and examined the potential regulation of HSD2 in the fetal lung by sex steroids. Human adult lung, fetal lung, and cultured fetal lung explant tissues contained similar amounts of HSD2 mRNA. However, higher levels of HSD2 protein were detected in human fetal lung tissue than in adult lung, with expression being restricted to a subset of epithelial cells in the fetal lung tissue. Differentiated fetal lung explants maintained in culture expressed higher levels of HSD2 protein and enzymatic activity than undifferentiated fetal lung tissues. Finally, HSD2 protein levels were decreased in male, but not female, fetal lung explants treated with 17-␤ estradiol. In contrast, 5-␣ dihydrotestosterone did not significantly affect HSD2 levels. These data indicate that HSD2 protein and activity levels increase in parallel with the differentiation of alveolar type II epithelial cells in vitro, and that HSD2 protein levels are regulated by 17-␤ estradiol in male fetal lung tissue. (Pediatr Res 62: 26-31, 2007)

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Insulin regulation of messenger ribonucleic acid for the surfactant- associated proteins in human fetal lung in vitro

Cited by 32 publications

References 0 publications

Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

Alveolarization in Retinoic Acid Receptor-β–Deficient Mice

11-β Hydroxysteroid Dehydrogenase Type 2 in Human Adult and Fetal Lung and Its Regulation by Sex Steroids

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