scholarly journals Protective effect of baicalin on fetal lung development in a rabbit model of congenital diaphragmatic hernia

Author(s):  
Hailong Su ◽  
Linsong Mu ◽  
Changsheng Liu
2022 ◽  
Author(s):  
Kasra Khalaj ◽  
Rebeca Lopes Figueira ◽  
Lina Antounians ◽  
Sree Gandhi ◽  
Matthew Wales ◽  
...  

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.


2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Francesca Maria Russo ◽  
Marina Gabriela Monteiro Carvalho Mori Da Cunha ◽  
Julio Jimenez ◽  
Flore Lesage ◽  
Mary Patrice Eastwood ◽  
...  

2008 ◽  
Vol 199 (6) ◽  
pp. S177
Author(s):  
Elisa Done ◽  
Léonardo Gucciardo ◽  
Lourenco Sbragia ◽  
Xenia Roubliova ◽  
Steffi Mayer ◽  
...  

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.


1995 ◽  
Vol 173 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Faith Kizilcan ◽  
F.Cahirt Tanyel ◽  
Nur Çakar ◽  
Nebil Büyükpamukçu ◽  
Akgün Hiçsönmez

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

2014 ◽  
Vol 49 (12) ◽  
pp. 1749-1752 ◽  
Author(s):  
Kohei Sakai ◽  
Osamu Kimura ◽  
Taizo Furukawa ◽  
Shigehisa Fumino ◽  
Koji Higuchi ◽  
...  

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