Prevention and Treatment of Bronchopulmonary Dysplasia: Contemporary Status and Future Outlook

Cerný, L; Torday, John S.; Rehan, Virender K.

doi:10.1007/s00408-007-9069-z

Cited by 55 publications

(45 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is essentially a disease of prematurity that is caused by a wide variety of proinflammatory factors, including barotrauma, oxotrauma, and infection (3,7,9,15,18). All these agonal insults seem to funnel through the common pathway leading to delayed alveolarization and myofibroblast proliferation (33).…”

Section: Discussionmentioning

confidence: 99%

Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Sakurai

Torday

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

Curcumin has potent antioxidant and anti-inflammatory properties, and it modulates signaling of peroxisome proliferator-activated receptor-␥ (PPAR␥), an important molecule in the pathobiology of BPD. However, its role in the prevention of BPD is not known. We determined 1) if curcumin enhances neonatal lung maturation, 2) if curcumin protects against hyperoxia-induced neonatal lung injury, and 3) if this protection is mediated by blocking TGF-␤. Embryonic day 19 fetal rat lung fibroblasts were exposed to 21% or 95% O 2 for 24 h following 1 h of treatment with curcumin. Curcumin dose dependently accelerated e19 fibroblast differentiation [increased parathyroid hormone-related protein (PTHrP) receptor, PPAR␥, and adipocyte differentiation-related protein (ADRP) levels and triolein uptake] and proliferation (increased thymidine incorporation). Pretreatment with curcumin blocked the hyperoxia-induced decrease (PPAR␥ and ADRP) and increase (␣-smooth muscle actin and fibronectin) in markers of lung injury/repair, as well as the activation of TGF-␤ signaling. In a separate set of experiments, neonatal Sprague-Dawley rat pups were exposed to 21% or 95% O 2 for 7 days with or without intraperitoneal administration of curcumin. Analysis for markers of lung injury/repair [PTHrP receptor, PPAR␥, ADRP, fibronectin, TGF-␤ receptor (activin receptor-like kinase 5), and Smad3] and lung morphology (radial alveolar count) demonstrated that curcumin effectively blocks TGF-␤ activation and hyperoxia-induced lung injury. Therefore, curcumin accelerates lung maturation by stimulating key alveolar epithelial-mesenchymal interactions and prevents hyperoxiainduced neonatal lung injury, possibly by blocking TGF-␤ activation, suggesting that it is a potential intervention against BPD. bronchopulmonary dysplasia; hyperoxia; transforming growth factor-␤ APPROXIMATELY 30% of premature infants with birth weights Ͻ1,000 g develop bronchopulmonary dysplasia (BPD) (15). The "new" BPD is characterized by abnormal lung cytoarchitecture, characterized by deranged alveolarization, with minimal large and small airway changes, and relatively mild inflammation and fibrosis (9). Infants with BPD are at significant risk of increased morbidity and mortality. They are unable to oxygenate efficiently and often require O 2 supplementation well into childhood. Although the pathogenesis of BPD is not completely understood, hyperoxia, inflammation, and/or ventilator exposure of the premature lung are the principal causative factors (33). More importantly, there is no effective intervention to prevent or treat BPD (3).Mesenchymal interstitial fibroblasts play an important role in lung development and injury/repair (16,34,36,38). During lung development and injury/repair, alveolar interstitial fibroblasts (AIFs) differentiate into lipid-laden AIFs (lipofibroblasts), which promote alveolar epithelial cell proliferation and differentiation (36). However, if AIFs lose their lipogenic phenotype and transdifferentiate to a myogenic phenotype, i.e., myofibroblasts, the...

show abstract

Section: Discussionmentioning

confidence: 99%

Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Sakurai

Torday

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

“…infants with BPD is reported every year in the United States (10), and accounts for 85% of all preterm complications. Due to lung damage at early developmental stages, these patients suffer with persistent respiratory complications beyond their childhood (11,12).…”

mentioning

confidence: 99%

Role of MicroRNA-150 and Glycoprotein Nonmetastatic Melanoma Protein B in Angiogenesis during Hyperoxia-Induced Neonatal Lung Injury

Narasaraju

Shukla

et al. 2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Glycoprotein nonmetastatic melanoma protein B (GPNMB), a transmembrane protein, has been reported to have an important role in tissue repair and angiogenesis. Recently, we have demonstrated that hyperoxia exposure down-regulates microRNA (miR)-150 expression and concurrent induction of its target gene, GPNMB, in neonatal rat lungs. This study aimed to test the hypothesis that soluble GPNMB (sGPNMB) promotes angiogenesis in the hyperoxic neonatal lungs. Wild-type (WT) or miR-150 knockout (KO) neonates, exposed to 95% O 2 for 3, 6, and 10 days, were evaluated for lung phenotypes, GPNMB protein expression in the lungs, and sGPNMB levels in the bronchoalveolar lavage. Angiogenic effects of sGPNMB were examined both in vitro and in vivo. After a 6-day exposure, similar analyses were performed in WT and miR-150 KO neonates during recovery at 7, 14, and 21 days. miR-150 KO neonates displayed an increased capillary network, decreased inflammation, and less alveolar damage compared with WT neonates after hyperoxia exposure. The early induction of GPNMB and sGPNMB were found in miR-150 KO neonates. The recombinant GPNMB, which contained a soluble portion of GPNMB, promoted endothelial tube formation in vitro and enhanced angiogenesis in vivo. The increased capillaries in the hyperoxic lungs of miR-150 KO neonates appeared dysmorphic. They were abnormally enlarged in size and occasionally laid at subepithelial regions in the alveoli. However, the lung architecture returned to normal during recovery, suggesting that abnormal vascularity during hyperoxia does not affect postnatal lung development. GPNMB plays an important role in angiogenesis during hyperoxia injury. Treatment with GPNMB may offer a novel therapeutic approach in reducing pathologic complications in bronchopulmonary dysplasia.

show abstract

“…2,10 Assim como relatado no artigo de Cogo et al, 11 os prematuros que desenvolveram a DBP no presente estudo, utilizaram concentrações de oxigênio mais altas que os não doentes. Porém, nesta pesquisa o valor médio da Displasia broncopulmonar em prematuros sob ventilação mecânica precoce FiO 2 foi inferior (0,47) quando comparado ao referido pelos autores (0,62).…”

Section: Discussionunclassified

“…A ocorrência de morbidades na evolução desses neonatos é frequente, sendo uma delas a Displasia Broncopulmonar (DBP), considerada uma das complicações crônicas mais importantes em prematuros sobreviventes. 1,2 Há uma relação inversa entre incidência da DBP com a idade gestacional e o peso ao nascimento da criança. 1,3 Em estudo multicêntrico realizado em países da America Latina com recém-nascidos entre 500 a 1500 gramas, a incidência da DBP foi 24,4%.…”

Section: Introductionunclassified

Fatores associados à displasia broncopulmonar em prematuros sob ventilação mecânica precoce

Duarte

Coutinho

2012

Rev. Bras. Saude Mater. Infant.

View full text Add to dashboard Cite

OBJETIVOS: descrever os fatores neonatais e de assistência ventilatória associados à displasia broncopulmonar (DBP), e verificar sua frequência em recém-nascidos prematuros submetidos à ventilação mecânica (VM) na primeira semana de vida. MÉTODOS: coorte retrospectiva, realizada em Unidade de Terapia Intensiva Neonatal. Foram analisados prontuários de 86 prematuros, sob VM na primeira semana de vida e registrados dados neonatais, parâmetros da VM e sua relação com a DBP. Para verificar a associação entre as variáveis do estudo e a DBP utilizou-se o teste do qui-quadrado e o Exato de Fisher quando indicado. O teste t e o Kruskal Wallis foram utilizados para a comparação das médias das variáveis contínuas. RESULTADOS: a DBP ocorreu em 17,4%. Foram relacionados à doença: menor peso ao nascer e idade gestacional, Apgar <7 no 1º e 5º minutos, maior tempo sob antibioticoterapia, nutrição parenteral e VM, valores elevados de fração inspirada de oxigênio (FiO2), VM como primeiro suporte respiratório, menor volume de nutrição enteral e ganho ponderal . Não houve diferença nos níveis de pressão positiva inspiratória, pressão positiva expiratória final e diferença de pressão. CONCLUSÕES: a ocorrência da DBP foi baixa e relacionada ao manejo clínico e nutricional e VM precoce e prolongada. Excetuando-se a FiO2 média não foi encontrada relação entre a doença e os demais parâmetros ventilatórios.

show abstract

Prevention and Treatment of Bronchopulmonary Dysplasia: Contemporary Status and Future Outlook

Cited by 55 publications

References 107 publications

Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling

Role of MicroRNA-150 and Glycoprotein Nonmetastatic Melanoma Protein B in Angiogenesis during Hyperoxia-Induced Neonatal Lung Injury

Fatores associados à displasia broncopulmonar em prematuros sob ventilação mecânica precoce

Contact Info

Product

Resources

About