STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxin-mediated lung injury

Ikegami, Machiko; Falcone, A.B.; Whitsett, Jeffrey A.

doi:10.1152/japplphysiol.00875.2007

Cited by 40 publications

(35 citation statements)

References 52 publications

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“…Finally, it is possible that the excess of SP-B may reflect an accumulation of surfactant subfractions particularly enriched in SP-B (19). The decrease of the SP-B (%PL) ratio along with clinical and respiratory improvements, were reasonably related with a better oxygenation status, which may represent the result of an improved clearance or a decreased secretion of SP-B.Our data are in line with previous results obtained both in animal studies (20,21) and in newborns after lung injury (22,23). Ikegami et al (20) found that in healthy mice (with normal lungs) the induction of lung injury by the intratracheal injection of LPS resulted in an increase of DSPC and SP-B, mediated by STAT-3, which is consistent with an acute response to the lung injury.…”

Section: Discussionsupporting

confidence: 91%

Surfactant protein B and A concentrations are increased in neonatal pneumonia

et al. 2015

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Background: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and illdefined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. Methods: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-13 C-PA)dipalmitoyl-phosphatidylcholine. results: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t 1/2 was significantly shorter in the pneumonia group (11.8 (5.5-19.8) h vs. 26.6 (19.3-63.6) h, P = 0.011). conclusion: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease's resolution is associated with the restoration of the normal ratio between SP-B and PL.

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Section: Discussionsupporting

confidence: 91%

Surfactant protein B and A concentrations are increased in neonatal pneumonia

et al. 2015

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“…AT2 cells synthesize surfactant phospholipids under control of the transcription factor STAT-3 (signal transducer and activator of transcription-3). Lung-specific deletion of STAT-3 decreases surfactant production and exacerbates ALI (125). AT2 cells store surfactant in vesicles termed lamellar bodies (LBs).…”

Section: Wwwannualreviewsorg • Repair Of the Alveolar-capillary Barmentioning

confidence: 99%

Regulation and Repair of the Alveolar-Capillary Barrier in Acute Lung Injury

Bhattacharya

Matthay

2013

Annu. Rev. Physiol.

288

208

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Considerable progress has been made in understanding the basic mechanisms that regulate fluid and protein exchange across the endothelial and epithelial barriers of the lung under both normal and pathological conditions. Clinically relevant lung injury occurs most commonly from severe viral and bacterial infections, aspiration syndromes, and severe shock. The mechanisms of lung injury have been identified in both experimental and clinical studies. Recovery from lung injury requires the reestablishment of an intact endothelial barrier and a functional alveolar epithelial barrier capable of secreting surfactant and removing alveolar edema fluid. Repair mechanisms include the participation of endogenous progenitor cells in strategically located niches in the lung. Novel treatment strategies include the possibility of cell-based therapy that may reduce the severity of lung injury and enhance lung repair.

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“…By intraperitoneal injection, Cebp␣ ⌬/⌬ and control mice in air and after 24-h exposure to hyperoxia (n ϭ 5/group) were given 10 l/g body wt containing 0.7 Ci [ 3 H]palmitic acid that was stabilized in 0.9% NaCl with 5% human serum albumin (25). Mice were continuously exposed to hyperoxia for hyperoxia group, or air for comparison group, and killed at 8 h after radiolabeled surfactant phospholipid precursor injection.…”

Section: Transgenic Mice Cebp␣mentioning

confidence: 99%

C/EBPα is required for pulmonary cytoprotection during hyperoxia

Xu¹,

Saegusa²,

Schehr³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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A number of transcriptional pathways regulating fetal lung development are active during repair of the injured lung. We hypothesized that C/EBPα, a transcription factor critical for lung maturation, plays a role in protection of the alveolar epithelium following hyperoxic injury of the mature lung. Transgenic CebpαΔ/Δmice, in which Cebpα was conditionally deleted from Clara cells and type II cells after birth, were developed. While no pulmonary abnormalities were observed in the CebpαΔ/Δmice (7–8 wk old) under normal conditions, the mice were highly susceptible to hyperoxia. CebpαΔ/Δmice died within 4 days of exposure to 95% oxygen in association with severe lung inflammation, altered maturation of surfactant protein B and C, decreased surfactant lipid secretion, and abnormal lung mechanics at a time when all control mice survived. mRNA microarray analysis of isolated type II cells at 0, 2, and 24 h of hyperoxia demonstrated the reduced expression of number of genes regulating surfactant lipid and protein homeostasis, including Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes influencing cell signaling or immune responses were induced in the lungs of CebpαΔ/Δmice. C/EBPα was required for the regulation of genes associated with surfactant lipid homeostasis, surfactant protein biosynthesis, processing and transport, defense response to stress, and cell redox homeostasis during exposure to hyperoxia. While C/EBPα did not play a critical role in postnatal pulmonary function under normal conditions, C/EBPα mediated protection of the lung during acute lung injury induced by hyperoxia.

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STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxin-mediated lung injury

Abstract: Ikegami M, Falcone A, Whitsett JA. STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxinmediated lung injury.

Cited by 40 publications

References 52 publications

Surfactant protein B and A concentrations are increased in neonatal pneumonia

Surfactant protein B and A concentrations are increased in neonatal pneumonia

Regulation and Repair of the Alveolar-Capillary Barrier in Acute Lung Injury

C/EBPα is required for pulmonary cytoprotection during hyperoxia

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