Early growth response factor-1 in acute lung injury

Ngiam, Nicola; Post, Martin; Kavanagh, Brian P.

doi:10.1152/ajplung.00265.2007

Cited by 34 publications

(19 citation statements)

References 29 publications

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“…Previous in vivo studies using adult rats (7), mice (20), and preterm fetal sheep (19) and in vitro studies using fetal rat lung epithelial cells (8) have demonstrated that Egr1 expression is upregulated in response to mechanical stress while its downregulation by carbon monoxide attenuates ventilator-induced lung injury (20). Thus Egr1 is an important proinflammatory transcriptional regulator that coordinates pro-inflammatory responses (38,48), including transcription of genes involved in growth and apoptosis (38), including FasL (22). Increased expression of both Egr1 and FasL in alveolar type II cells after ventilation suggests that Egr1 may activate the extrinsic caspase pathway via upregulation of FasL.…”

Section: Discussionmentioning

confidence: 99%

Mechanical ventilation-induced apoptosis in newborn rat lung is mediated via FasL/Fas pathway

Kroon

DelRiccio

Tseu

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Aim To determine whether the immediate bolus strategy treatment could decrease the subsequent need for ventilation compared to the administration of surfactant prophylaxis at 15-minutes. Methods All infants born before 29 weeks', and infants born at 29 to 30 weeks' without antenatal steroid(ANS) were randomized. Infants of group-1 were intubated immediately after birth, of group-2 received standard resuscitation measures, than were intu-bated at 15-minutes. All received 100 mg/kg surfactant. During these managements infants were ventilated with T-piece(NeoPuff). Then infants were extubated to NCPAP(Infant Flow®) if respiratory drive was present. The primary outcome was the need for MV within the first 3-days of life. The secondary outcomes were neona-tal morbidities, mortality and duration of hospitalization. Results Total of 80 newborns were enrolled (fourty infants in each group). Prenatal and natal features were similar in groups. Ten infants in group-1, 13 infants in group-2 couldn't be extubated after surfactant. GA and BW of them were lower than the extubated infants. Six infants in group-1, four infants in group-2 needed MV during the first 3-days. Total respiratory support duration was lower in group-1. There were no significant differences between the groups with a respect to PDA, NEC, IVH, sepsis, ROP, BPD, mortality and duration of hospitalization. Conclusion Our study didn't demonstrate a superiority of the immediate bolus strategy of surfactant prophylaxis combined with early-NCPAP to the administration of surfactant at 15-minutes after birth with early-NCPAP. Surfactant prophylaxis at-15 minutes with early-NCPAP seems to be sufficiently effective to yield favorable outcomes in small preterm infants. Rationale Mechanical ventilation induces pulmonary apoptosis and inhibits alveolar development in preterm infants, but the molecular basis for this apoptotic injury is unknown. Objective To determine the signaling mechanism(s) of ventilation(stretch)-induced apoptosis in newborn rat lung. Methods Seven-day old rats were ventilated with room air for 24 h using moderate tidal volumes (8.5 mL.kg-1). Isolated fetal rat lung epithelial and fibroblast cells were subjected to continuous cyclic stretch (5, 10 or 17% elongation) for up to 12 h. Measurements and main results Prolonged ventilation increased significantly the number of apoptotic alveolar type II cells (i.e. TUNEL-labelling, anti-cleaved caspase-3 immunochemistry) and was associated with increased expression of the apoptotic mediator Fas Ligand (FasL). Fetal lung epithelial cells, but not fibroblasts, subjected to maximal (i.e. 17%, but not lesser elongation) cyclic stretch exhibited increased apoptosis (i.e. nuclear fragmentation; DNA laddering) which appeared to be mediated via the extrinsic pathway (increased expression of FasL and cleaved caspase-3,-7 and-8). The intrinsic pathway appeared not to be involved (minimal mitochondrial 232 233 Background and aims Insulin is frequently required to treat hyperglycemia that increases both mortality and ...

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Section: Discussionmentioning

confidence: 99%

Mechanical ventilation-induced apoptosis in newborn rat lung is mediated via FasL/Fas pathway

Kroon

DelRiccio

Tseu

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Stretch injury causes Egr-1 activation through MAP kinase phosphorylization (36). Egr-1 signaling, as seen in these animals, can then activate a variety of pathways, including proinflammatory cytokines (37). Initiation of ventilation in preterm sheep also increases multiple early response genes, including CYR61 and CTGF (46).…”

Section: Discussionmentioning

confidence: 99%

Inflammation and lung maturation from stretch injury in preterm fetal sheep

Hillman

Polglase

Pillow

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…7,8 As a transcriptional master regulator that integrates converging signaling pathways, Egr-1 has a central role in orchestrating adaptive cellular response to injury. 9 Because of its significance in cardiovascular pathobiology, the regulation of Egr-1 in the vascular system has been investigated extensively. In vascular smooth muscle cells, TGF-␤ was shown to induce Egr-1 via the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) pathway.…”

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confidence: 99%

Smad-Independent Transforming Growth Factor-β Regulation of Early Growth Response-1 and Sustained Expression in Fibrosis

Bhattacharyya

Chen

et al. 2008

The American Journal of Pathology

110

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Transforming growth factor-␤ (TGF-␤) plays a key role in scleroderma pathogenesis. The transcription factor early growth response-1 (Egr-1) mediates the stimulation of collagen transcription elicited by TGF-␤ and is necessary for the development of pulmonary fibrosis in mice. Here, we report that TGF-␤ causes a time-and dose-dependent increase in Egr-1 protein and mRNA levels and enhanced transcription of the Egr-1 gene via serum response elements in normal fibroblasts. The ability of TGF-␤ to stimulate Egr-1 was preserved in Smad3-null mice and in explanted Smad3-null fibroblasts. The response was blocked by a specific mitogen-activated protein kinase kinase 1 (MEK1) inhibitor but not by an ALK5 kinase inhibitor. Furthermore, MEK1 was phosphorylated by TGF-␤, which was sufficient to drive Egr-1 transactivation. Stimulation by TGF-␤ enhanced the transcriptional activity of Elk-1 via the MEK-extracellular signal-regulated kinase 1/2 pathway. Bleomycininduced scleroderma in the mouse was accompanied by increased Egr-1 accumulation in lesional fibroblasts. Furthermore, biopsies of lesional skin and lung from patients with scleroderma showed increased Egr-1 levels, which were highest in early diffuse disease. Moreover, both Egr-1 mRNA and protein were elevated in explanted scleroderma skin fibroblasts in vitro. Together, these findings define a Smadindependent TGF-␤ signal transduction mechanism that underlies the stimulation of Egr-1, demonstrate for the first time sustained Egr-1 up-regulation in fibrotic lesions and suggests that Egr-1 has a role in the induction and progression of fibrosis.

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Early growth response factor-1 in acute lung injury

Cited by 34 publications

References 29 publications

Mechanical ventilation-induced apoptosis in newborn rat lung is mediated via FasL/Fas pathway

Mechanical ventilation-induced apoptosis in newborn rat lung is mediated via FasL/Fas pathway

Inflammation and lung maturation from stretch injury in preterm fetal sheep

Smad-Independent Transforming Growth Factor-β Regulation of Early Growth Response-1 and Sustained Expression in Fibrosis

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