Lung liquid, fetal lung growth, and congenital diaphragmatic hernia

1995 ◽  
Vol 10 (1) ◽  
Author(s):  
JohnW. DiFiore ◽  
JayM. Wilson
2005 ◽  
Vol 21 (1) ◽  
pp. 39-44 ◽  
Author(s):  
F. Bargy ◽  
S. Beaudoin ◽  
P. Barbet

2008 ◽  
Vol 144 (2) ◽  
pp. 324
Author(s):  
Shaun A. Steigman ◽  
Melissa J. Hayward ◽  
Shaun M. Kunisaki ◽  
Michael J. Giuffrida ◽  
Y. Avery Ching ◽  
...  

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ana N. Gonçalves ◽  
Jorge Correia-Pinto ◽  
Cristina Nogueira-Silva

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.


2017 ◽  
Vol 45 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Paulina Piairo ◽  
Rute S. Moura ◽  
Maria João Baptista ◽  
Jorge Correia-Pinto ◽  
Cristina Nogueira-Silva

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.


Author(s):  
Eugenia Antolin ◽  
Roberto Rodriguez ◽  
Jose Luis Encinas ◽  
Beatriz Herrero ◽  
Marta Muner ◽  
...  

2013 ◽  
Vol 48 (6) ◽  
pp. 1165-1171 ◽  
Author(s):  
Irving J. Zamora ◽  
Darrell L. Cass ◽  
Timothy C. Lee ◽  
Stephen Welty ◽  
Christopher I. Cassady ◽  
...  

2014 ◽  
Vol 35 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Alan Coleman ◽  
Nisarat Phithakwatchara ◽  
Aimen Shaaban ◽  
Sundeep Keswani ◽  
Beth Kline-Fath ◽  
...  

2010 ◽  
Vol 31 (4) ◽  
pp. 269-273 ◽  
Author(s):  
K Terui ◽  
A Omoto ◽  
H Osada ◽  
T Hishiki ◽  
T Saito ◽  
...  

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