scholarly journals Overexpression of Spock2 in mice leads to altered lung alveolar development and worsens lesions induced by hyperoxia

2020 ◽  
Vol 319 (1) ◽  
pp. L71-L81 ◽  
Author(s):  
Alice Hadchouel ◽  
Marie-Laure Franco-Montoya ◽  
Sophie Guerin ◽  
Marcio Do Cruzeiro ◽  
Mickaël Lhuillier ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Transgenic Mouse Model ◽  
Matrix Metalloproteinase 2 ◽  
Preterm Neonates ◽  
Alveolar Cells ◽  
Very Preterm ◽  
Rat Pups ◽  
Alveolar Development

SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 ( SPOCK2) was previously associated with genetic susceptibility to bronchopulmonary dysplasia in a French population of very preterm neonates. Its expression increases during lung development and is increased after exposure of rat pups to hyperoxia compared with controls bred in room air. To further investigate the role of SPOCK2 during lung development, we designed two mouse models, one that uses a specific anti-Spock2 antibody and one that reproduces the hyperoxia-induced Spock2 expression with a transgenic mouse model resulting in a conditional and lung-targeted overexpression of Spock2. When mice were bred under hyperoxic conditions, treatment with anti-Spock2 antibodies significantly improved alveolarization. Lung overexpression of Spock2 altered alveolar development in pups bred in room air and worsened hyperoxia-induced lesions. Neither treatment with anti-Spock2 antibody nor overexpression of Spock2 was associated with abnormal activation of matrix metalloproteinase-2. These two models did not alter the expression of known players in alveolar development. This study brings strong arguments for the deleterious role of SPOCK2 on lung alveolar development especially after lung injury, suggesting its role in bronchopulmonary dysplasia susceptibility. These effects are not mediated by a deregulation in metalloproteases activity and in expression of factors essential to normal alveolarization. The balance between types 1 and 2 epithelial alveolar cells may be involved.

scholarly journals Effects of Hyperoxia on Mitochondrial Homeostasis: Are Mitochondria the Hub for Bronchopulmonary Dysplasia?

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Xuefei ◽  
Zhao Xinyi ◽  
Cai Qing ◽  
Zhang Dan ◽  
Liu Ziyun ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Redox Reactions ◽  
Rodent Models ◽  
Cell Plasticity ◽  
Mitochondrial Homeostasis ◽  
Alveolar Development ◽  
Lung Structure ◽  
Neonatal Lung ◽  
High Concentrations

Mitochondria are involved in energy metabolism and redox reactions in the cell. Emerging data indicate that mitochondria play an essential role in physiological and pathological processes of neonatal lung development. Mitochondrial damage due to exposure to high concentrations of oxygen is an indeed important factor for simplification of lung structure and development of bronchopulmonary dysplasia (BPD), as reported in humans and rodent models. Here, we comprehensively review research that have determined the effects of oxygen environment on alveolar development and morphology, summarize changes in mitochondria under high oxygen concentrations, and discuss several mitochondrial mechanisms that may affect cell plasticity and their effects on BPD. Thus, the pathophysiological effects of mitochondria may provide insights into targeted mitochondrial and BPD therapy.

scholarly journals Oxidative and Proteolytic Inactivation of Alpha-1 Antitrypsin in Bronchopulmonary Dysplasia Pathogenesis: A Top-Down Proteomic Bronchoalveolar Lavage Fluid Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Chiara Tirone ◽  
Federica Iavarone ◽  
Milena Tana ◽  
Alessandra Lio ◽  
Claudia Aurilia ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchopulmonary Dysplasia ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Small Sample ◽  
Preterm Neonates ◽  
Ionization Mass ◽  
Top Down ◽  
Alpha 1 Antitrypsin

The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25–57, 375–418, 397–418, 144–171, and 397–418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397–418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.

Role of the Nrf2/HO-1 axis in bronchopulmonary dysplasia and hyperoxic lung injuries

2017 ◽  
Vol 131 (14) ◽  
pp. 1701-1712 ◽  
Author(s):  
Emanuele Amata ◽  
Valeria Pittalà ◽  
Agostino Marrazzo ◽  
Carmela Parenti ◽  
Orazio Prezzavento ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Relevant Literature ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Neurodevelopmental Delay ◽  
Lung Injuries ◽  
Life Threatening ◽  
Preterm Newborns

Bronchopulmonary dysplasia (BPD) is a chronic illness that usually originates in preterm newborns. Generally, BPD is a consequence of respiratory distress syndrome (RDS) which, in turn, comes from the early arrest of lung development and the lack of pulmonary surfactant. The need of oxygen therapy to overcome premature newborns’ compromised respiratory function generates an increasing amount of reactive oxygen species (ROS), the onset of sustained oxidative stress (OS) status, and inflammation in the pulmonary alveoli deputies to respiratory exchanges. BPD is a severe and potentially life-threatening disorder that in the most serious cases, can open the way to neurodevelopmental delay. More importantly, there is no adequate intervention to hamper or treat BPD. This perspective article seeks to review the most recent and relevant literature describing the very early stages of BPD and hyperoxic lung injuries focussing on nuclear factor erythroid derived 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. Indeed, Nrf2/HO1 activation in response to OS induced lung injury in preterm concurs to the induction of certain number of antioxidant, anti-inflammatory, and detoxification pathways that seem to be more powerful than the activation of one single antioxidant gene. These elicited protective effects are able to counteract/mitigate all multifaceted aspects of the disease and may support novel approaches for the management of BPD.

Neurodevelopmental outcomes in very preterm infants: The role of severity of Bronchopulmonary Dysplasia

2021 ◽  
Vol 152 ◽  
pp. 105275
Author(s):  
Francesca Gallini ◽  
Maria Coppola ◽  
Domenico Umberto De Rose ◽  
Luca Maggio ◽  
Roberta Arena ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Neurodevelopmental Outcomes ◽  
Very Preterm Infants ◽  
Very Preterm

scholarly journals Reference: The role of corticosteroids in a preterm infant with lung pathology in the first three months of life.

2021 ◽  
Author(s):  
Femi Adeniyi
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Scientific Evidence ◽  
Extensive Study ◽  
Preterm Neonates ◽  
Lung Pathology ◽  
Selective Treatment ◽  
Term Outcome ◽  
Long Term Outcome

Corticosteroids are helpful in the treatment of preterm neonates at risk of bronchopulmonary dysplasia (BPD). However, its usefulness depends on patient selection, the timing of intervention with a corticosteroid, and choice of corticosteroid. In making these clinical choices, one must consider both short and long-term outcomes. Although corticosteroid use has been available for decades in preterm neonatal care, many aspects of corticosteroid use are unresolved due to limited research. Corticosteroids cause upregulation of anti-inflammatory, inhibiting pro-inflammatory mediators at the genomic level. Furthermore, the benefits of using corticosteroids should outweigh the known risks. Here we will discuss the current literature to guide clinical practice—a literature search for evidence through the clinical database on EMBASE, Medline, PubMed, and Cochrane. The keywords are bronchopulmonary dysplasia, corticosteroids, and prematurity.Limitations.There is bias due to limited research available to provide a high level of scientific evidence on the use of different modes of administration, other agents compared to the systemic use of dexamethasone. Conclusion.The consensus in the prevention of BPD is selective treatment after one week of life with dexamethasone. There is limited evidence to suggest the role of prophylaxis hydrocortisone in preventing BPD and advise to be considered in centers with a high risk of BPD. An extensive study into prophylaxis hydrocortisone for prevention of BDP and long-term outcome appears to be promising.The role of instilled steroids with surfactants at birth appears promising in the single-center study. A multicentre double-blinded randomized intratracheal budesonide use at delivery will be valuable.

Role of the Central Venous Catheter in Bloodstream Infections Caused by Coagulase-negative Staphylococci in Very Preterm Neonates

2013 ◽  
Vol 32 (6) ◽  
pp. 622-628 ◽  
Author(s):  
Margaux Lepainteur ◽  
Marine Desroches ◽  
Anne Sophie Bourrel ◽  
Said Aberrane ◽  
Vincent Fihman ◽  
...  
Keyword(s):  
Central Venous Catheter ◽  
Bloodstream Infections ◽  
Venous Catheter ◽  
Preterm Neonates ◽  
Central Venous ◽  
Coagulase Negative Staphylococci ◽  
Very Preterm

scholarly journals N-Terminal Pro-B Type Natriuretic Peptide as a Marker of Bronchopulmonary Dysplasia or Death in Very Preterm Neonates: A Cohort Study

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140079 ◽  
Author(s):  
Anna Sellmer ◽  
Vibeke Elisabeth Hjortdal ◽  
Jesper Vandborg Bjerre ◽  
Michael Rahbek Schmidt ◽  
Patrick J. McNamara ◽  
...  
Keyword(s):  
Cohort Study ◽  
Natriuretic Peptide ◽  
Bronchopulmonary Dysplasia ◽  
Preterm Neonates ◽  
Very Preterm

scholarly journals Stability of the Glutathione Supplementation into Parenteral Nutrition to Protect Very Preterm Babies from Oxidative Stress

2021 ◽  
Author(s):  
Clémence Guiraut ◽  
Nadine El Raichani ◽  
Guillaume Morin ◽  
Ibrahim Mohamed ◽  
Jean-Claude Lavoie
Keyword(s):  
Oxidative Stress ◽  
Parenteral Nutrition ◽  
Bronchopulmonary Dysplasia ◽  
Preterm Neonates ◽  
Maximum Loss ◽  
Very Preterm ◽  
Premature Babies ◽  
Therapeutic Benefits ◽  
Preterm Babies ◽  
Glutathione Deficiency

Most very premature newborns (< 32 weeks of gestation) receive parenteral nutrition (PN) that is inherently contaminated with peroxides. Oxidative stress induced by PN is associated with bronchopulmonary dysplasia, a main pathological complication in these babies who have weak antioxidant capacity to detoxify peroxides because of their glutathione deficiency. In animals, glutathione supplementation of PN prevented oxidative stress and alveolar loss (the main characteristic of bronchopulmonary dysplasia). Of its two forms - disulfide (GSSG) and free thiol (GSH) - GSSG was used because of its better stability in PN. However, a 30% loss of GSSG in PN is observed. The potentially high therapeutic benefits of GSSG supplementation on the health of very premature babies makes the study of its stability highly important. Thus, GSSG was incubated in combination with the following components of PN: dextrose, multivitamins, Primene, Travasol, as well as with cysteine, cystine and peroxides for 24h. Total glutathione in these solutions was measured 0-24h after the addition of GSSG. The combination of cysteine and multivitamins caused the maximum loss of glutathione. Removing the cysteine prevented the degradation of glutathione. GSSG reacts with cysteine to form cysteine-glutathione disulfide, another suitable glutathione substrate for preterm neonates.

scholarly journals MicroRNA 29 Family Serves a Key Role in Lung Development and the Prevention of Lung Pathology

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A507-A507
Author(s):  
Ritu Mishra ◽  
Carole R Mendelson
Keyword(s):  
Cell Differentiation ◽  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Lung Fibrosis ◽  
Molecular Mechanisms ◽  
Clinical Medicine ◽  
Lung Pathology ◽  
Type Ii ◽  
Type Ii Cell

Abstract Even with remarkable advances in the care of preterm infants, chronic lung disease in the form of bronchopulmonary dysplasia (BPD) continues to be a significant pathologic consequence of prematurity. BPD is caused by the interruption of physiologic lung development and exposure of the immature newborn lung to high O2 tensions. BPD is characterized by a simplified alveolar structure, arrested lung growth, impaired vascular development and lung fibrosis (1). To identify effective treatment strategies for BPD, it is important to understand the molecular mechanisms underlying this disorder. MicroRNAs (miRNA, miR) are known to regulate growth, development and repair of the developing lung; whereas, dysregulation of miRNA expression has been associated with pulmonary disease. Specifically, members of the miR-29 family have been linked to pulmonary cancers, fibrosis, and BPD. Previous studies from our laboratory indicate that developmental induction of miR-29 expression in the fetal lung near term serves a key role in promoting surfactant-producing type II cell differentiation and function through repression of TGF-β2 signaling (2). To understand the role of miR-29 in protection against BPD, in the present study, we created mice in which the entire miR-29 family (miR-29a/b1 and miR-29b2/c) (miR-29 dKO) was disrupted. Upon exposure of miR-29 dKO and WT neonatal mice to hyperoxia (95% O2) for 5 days immediately after birth, expression levels of the proinflammatory cytokines and chemokines, IL-1 β, TGF-β1, CXCL2 and IL-6, were significantly increased in the lungs of miR-29 dKO mice, compared to WT. Furthermore, lungs of miR-29 dKO adult mice manifested increased expression of their direct targets, TGF-β2 and TGF-β3. This was associated with increased collagen deposition, as evidenced by enhanced trichrome staining, suggesting the development of lung fibrosis. HDAC4 (a direct target of miR-29) and proinflammatory TNF-α, which have been implicated in pulmonary fibrosis, also were upregulated in the lungs of miR-29 dKO mice. Overall, our studies suggest a key role of the miR-29 family and its targets in prevention of inflammatory and profibrotic signaling in the neonatal lung leading to lung pathology. Supported by: NIH R01-HL050022 (C.R.M.) References: (1)Michael, Zoe, et al. “Bronchopulmonary dysplasia: an update of current pharmacologic therapies and new approaches.” Clinical Medicine Insights: Pediatrics 12 (2018): 1179556518817322.(2)Guo, Wei, Houda Benlhabib, and Carole R. Mendelson. “The microRNA 29 family promotes type II cell differentiation in developing lung.” Molecular and cellular biology 36.16 (2016): 2141-2141.

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