Fetal Lung Growth in Congenital Diaphragmatic Hernia

2005 ◽  
Vol 21 (1) ◽  
pp. 39-44 ◽  
Author(s):  
F. Bargy ◽  
S. Beaudoin ◽  
P. Barbet
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Fetal Lung ◽  
Lung Growth

scholarly journals ROBO2 signaling in lung development regulates SOX2/SOX9 balance, branching morphogenesis and is dysregulated in nitrofen-induced congenital diaphragmatic hernia

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ana N. Gonçalves ◽  
Jorge Correia-Pinto ◽  
Cristina Nogueira-Silva
Keyword(s):  
Western Blot ◽  
Congenital Diaphragmatic Hernia ◽  
Progenitor Cells ◽  
Expression Profile ◽  
Diaphragmatic Hernia ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Lung Growth

Abstract Background Characterized by abnormal lung growth or maturation, congenital diaphragmatic hernia (CDH) affects 1:3000 live births. Cellular studies report proximal (SOX2+) and distal (SOX9+) progenitor cells as key modulators of branching morphogenesis and epithelial differentiation, whereas transcriptome studies demonstrate ROBO/SLIT as potential therapeutic targets for diaphragm defect repair in CDH. In this study, we tested the hypothesis that (a) experimental-CDH could changes the expression profile of ROBO1, ROBO2, SOX2 and SOX9; and (b) ROBO1 or ROBO2 receptors are regulators of branching morphogenesis and SOX2/SOX9 balance. Methods The expression profile for receptors and epithelial progenitor markers were assessed by Western blot and immunohistochemistry in a nitrofen-induced CDH rat model. Immunohistochemistry signals by pulmonary structure were also quantified from embryonic-to-saccular stages in normal and hypoplastic lungs. Ex vivo lung explant cultures were harvested at E13.5, cultures during 4 days and treated with increasing doses of recombinant rat ROBO1 or human ROBO2 Fc Chimera proteins for ROBO1 and ROBO2 inhibition, respectively. The lung explants were analyzed morphometrically and ROBO1, ROBO2, SOX2, SOX9, BMP4, and β-Catenin were quantified by Western blot. Results Experimental-CDH induces distinct expression profiles by pulmonary structure and developmental stage for both receptors (ROBO1 and ROBO2) and epithelial progenitor markers (SOX2 and SOX9) that provide evidence of the impairment of proximodistal patterning in experimental-CDH. Ex vivo functional studies showed unchanged branching morphogenesis after ROBO1 inhibition; increased fetal lung growth after ROBO2 inhibition in a mechanism-dependent on SOX2 depletion and overexpression of SOX9, non-phospho β-Catenin, and BMP4. Conclusions These studies provided evidence of receptors and epithelial progenitor cells which are severely affected by CDH-induction from embryonic-to-saccular stages and established the ROBO2 inhibition as promoter of branching morphogenesis through SOX2/SOX9 balance.

scholarly journals STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia

2017 ◽  
Vol 45 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Paulina Piairo ◽  
Rute S. Moura ◽  
Maria João Baptista ◽  
Jorge Correia-Pinto ◽  
Cristina Nogueira-Silva
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Lung Development ◽  
Pulmonary Hypoplasia ◽  
Fetal Lung ◽  
Developmental Expression ◽  
Lung Growth ◽  
Growth Modulation ◽  
Late Expression

Background: Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. Methods: We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Results: Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. Conclusion: These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH.

Patterns of fetal lung growth in fetuses with isolated left-sided congenital diaphragmatic hernia

2015 ◽  
pp. 1-8
Author(s):  
Eugenia Antolin ◽  
Roberto Rodriguez ◽  
Jose Luis Encinas ◽  
Beatriz Herrero ◽  
Marta Muner ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Fetal Lung ◽  
Lung Growth

The presence of a hernia sac in congenital diaphragmatic hernia is associated with better fetal lung growth and outcomes

2013 ◽  
Vol 48 (6) ◽  
pp. 1165-1171 ◽  
Author(s):  
Irving J. Zamora ◽  
Darrell L. Cass ◽  
Timothy C. Lee ◽  
Stephen Welty ◽  
Christopher I. Cassady ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Fetal Lung ◽  
Lung Growth ◽  
Hernia Sac

Fetal lung growth represented by longitudinal changes in MRI-derived fetal lung volume parameters predicts survival in isolated left-sided congenital diaphragmatic hernia

2014 ◽  
Vol 35 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Alan Coleman ◽  
Nisarat Phithakwatchara ◽  
Aimen Shaaban ◽  
Sundeep Keswani ◽  
Beth Kline-Fath ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Lung Volume ◽  
Fetal Lung ◽  
Lung Growth ◽  
Longitudinal Changes

scholarly journals Prediction of postnatal outcomes in congenital diaphragmatic hernia using MRI signal intensity of the fetal lung

2010 ◽  
Vol 31 (4) ◽  
pp. 269-273 ◽  
Author(s):  
K Terui ◽  
A Omoto ◽  
H Osada ◽  
T Hishiki ◽  
T Saito ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Signal Intensity ◽  
Fetal Lung

scholarly journals Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

2022 ◽  
Author(s):  
Kasra Khalaj ◽  
Rebeca Lopes Figueira ◽  
Lina Antounians ◽  
Sree Gandhi ◽  
Matthew Wales ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Congenital Diaphragmatic Hernia ◽  
Extracellular Vesicles ◽  
Diaphragmatic Hernia ◽  
Lung Development ◽  
Pulmonary Hypoplasia ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Neuroendocrine Cells ◽  
Beta Catenin

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, beta-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages, and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.

Sign in / Sign up

Export Citation Format

Share Document