Responses of Pulmonary Platelet-Derived Growth Factor Peptides and Receptors to Hyperoxia and Nitric Oxide in Piglet Lungs

Zhang, Xiaoming; Reinsvold, Patrick F; Thibeault, Donald W.; Ekekezie, Ikechukwu I; Rezaiekhaligh, Mo; Mabry, Sherry M; Buch, Shilpa; Truog, William E.

doi:10.1203/01.pdr.0000155762.91748.8d

Cited by 6 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the potential role of these factors in the pathophysiology of BPD, little is known about their changes in the injured neonatal lung, and even less about the possible preventive effects of NO on these changes. Hyperoxia has been shown to decrease mRNA expression of FGFR4 (19) and tropoelastin (2), whereas PDGFA did not change in a model of hyperoxia in piglet (20). Although no data are available in lung, NO has been shown to regulate basic FGF (bFGF) in muscle cells (21).…”

mentioning

confidence: 99%

Nitric Oxide Donor Restores Lung Growth Factor and Receptor Expression in Hyperoxia-Exposed Rat Pups

López

Boucherat

Franco-Montoya

et al. 2006

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Exposure of newborn rats to hyperoxia impairs alveolarization. Nitric oxide (NO) may prevent this evolution. Angiogenesis and factors involved in this process, but also other growth factors (GFs) involved in alveolar development, are likely potential therapeutic targets for NO. We studied the effects of the NO donor, [Z]-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1, 2-diolate, also termed DETANONOate (D-NO), on hyperoxia-induced changes in key regulatory factors of alveolar development in neonatal rats, and its possible preventive effect on the physiologic consequences of hyperoxia. Newborn rat pups were randomized at birth to hyperoxia (> 95% O2) or room air exposure for 6 or 10 d, while receiving D-NO or its diluent. On Day 6, several GFs and their receptors were studied at pre- and/or post-translational levels. Elastin transcript determination on Day 6, and elastin deposition in tissue and morphometric analysis of the lungs on Day 10, were also performed. Hyperoxia decreased the expression of vascular endothelial growth factor (VEGF) receptor (VEGFR) 2, fibroblast growth factor (FGF)-18, and FGF receptors (FGFRs) FGFR3 and FGFR4, increased mortality, and impaired alveolarization and capillary growth. D-NO treatment of hyperoxia-exposed pups restored the expression level of FGF18 and FGFR4, induced an increase of both VEGF mRNA and protein, enhanced elastin expression, and partially restored elastin deposition in alveolar walls. Although, under the present conditions, D-NO failed to prevent the physiologic consequences of hyperoxia in terms of survival and lung alveolarization, our findings demonstrate molecular effects of NO on GFs involved in alveolar development that may have contributed to the protective effects previously reported for NO.

show abstract

mentioning

confidence: 99%

Nitric Oxide Donor Restores Lung Growth Factor and Receptor Expression in Hyperoxia-Exposed Rat Pups

López

Boucherat

Franco-Montoya

et al. 2006

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…In this study, we determined the levels of VEGF, PDGF-A, and PDGF-B expression and elucidated the mechanisms that mediate the MSCs' effects because their mRNA and protein expression decreased in the lungs of newborn animals exposed to 14 days of hyperoxia [22][23][24]. VEGF is a potent endothelial cell mitogen that regulates angiogenesis and alveolar development [25].…”

Section: Discussionmentioning

confidence: 99%

Consecutive Daily Administration of Intratracheal Surfactant and Human Mesenchymal Stem Cells Attenuates Hyperoxia-induced Lung Injury in Neonatal Rats

Chou

Chang

Chen³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury. Surfactant reduced the in vitro viability of human MSCs, and the combination therapy of surfactant and MSCs did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The effects of 2 consecutive days of intratracheal administration of surfactant and MSCs on hyperoxia-induced lung injury were undetermined. Methods: Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or human MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + MSCs (3 × 104 cells), and O2 + surfactant + MSCs (3 × 105 cells). The lungs were excised for analysis on postnatal day 14.Results: The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and cytokine levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokine levels and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + MSCs (3 × 104 cells) group did.Conclusions: Consecutive daily administration of intratracheal surfactant and MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

show abstract

“…PDGF is crucial for alveolarization of the normally developing lung (31). We determined VEGF and PDGF-B expression as their mRNA and protein expression was decreased in the hyperoxia-exposed neonatal mice and piglet lungs (32, 33). In this study, we demonstrated that rats in the carrier protein + O 2 group exhibited significantly decreased VEGF and PDGF-B expression than those in the carrier protein + RA or Tn vaccine + RA group.…”

Section: Discussionmentioning

confidence: 99%

Maternal Tn Immunization Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats Through Suppression of Oxidative Stress and Inflammation

2019

View full text Add to dashboard Cite

Hyperoxia therapy is often required to treat newborns with respiratory disorders. Prolonged hyperoxia exposure increases oxidative stress and arrests alveolar development in newborn rats. Tn antigen is N-acetylgalactosamine residue that is one of the most remarkable tumor-associated carbohydrate antigens. Tn immunization increases the serum anti-Tn antibody titers and attenuates hyperoxia-induced lung injury in adult mice. We hypothesized that maternal Tn immunizations would attenuate hyperoxia-induced lung injury through the suppression of oxidative stress in neonatal rats. Female Sprague–Dawley rats (6 weeks old) were intraperitoneally immunized five times with Tn (50 μg/dose) or carrier protein at biweekly intervals on 8, 6, 4, 2, and 0 weeks before the day of delivery. The pups were reared in room air (RA) or 2 weeks of 85% O 2 , creating the four study groups: carrier protein + RA, Tn vaccine + RA, carrier protein + O 2 , and Tn vaccine + O 2 . The lungs were excised for oxidative stress, cytokine, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression, and histological analysis on postnatal day 14. Blood was withdrawn from dams and rat pups to check anti-Tn antibody using western blot. We observed that neonatal hyperoxia exposure reduced the body weight, increased 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and lung cytokine (interleukin-4), increased mean linear intercept (MLI) values, and decreased vascular density and VEGF and PDGF-B expressions. By contrast, Tn immunization increased maternal and neonatal serum anti-Tn antibody titers on postnatal day 14, reduced MLI, and increased vascular density and VEGF and PDGF-B expressions to normoxic levels. Furthermore, the alleviation of lung injury was accompanied by a reduction in lung cytokine and 8-OHdG expression. Therefore, we propose that maternal Tn immunization attenuates hyperoxia-induced lung injury in neonatal rats through the suppression of oxidative stress and inflammation.

show abstract

Responses of Pulmonary Platelet-Derived Growth Factor Peptides and Receptors to Hyperoxia and Nitric Oxide in Piglet Lungs

Cited by 6 publications

References 37 publications

Nitric Oxide Donor Restores Lung Growth Factor and Receptor Expression in Hyperoxia-Exposed Rat Pups

Nitric Oxide Donor Restores Lung Growth Factor and Receptor Expression in Hyperoxia-Exposed Rat Pups

Consecutive Daily Administration of Intratracheal Surfactant and Human Mesenchymal Stem Cells Attenuates Hyperoxia-induced Lung Injury in Neonatal Rats

Maternal Tn Immunization Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats Through Suppression of Oxidative Stress and Inflammation

Contact Info

Product

Resources

About