<scp>MicroRNA</scp> 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia

Eastwood, Patrice; Deprest, Jan; Russo, Francesca Maria; Wang, Hongmei; Mulhall, Drew; Mahood, Thomas H.; Keijzer, Richard

doi:10.1002/pd.5318

Cited by 16 publications

(12 citation statements)

References 35 publications

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“…miR-200b was also upregulated in the rabbit model of CDH, however, variable changes in miR-200b expression were identified following TO [64]. In the rodent model of CDH, miR-200b expression was dependent on both the region of lung tissue and stage of lung development.…”

Section: E Rt-qpcr Resultsmentioning

confidence: 93%

“…Despite the benefits of the rabbit model of CDH, it has been under-utilized and remains outnumbered by nitrofen-induced rodent models of CDH due to increased cost and technical difficulty. Of the published rabbit CDH papers, only a few have studied the effects of TO, and to the best of our knowledge, none have studied the impact of CDH and potential rescue effects of TO on the Wnt signaling pathway [43,64,65] (Figure 20).…”

Section: E Rt-qpcr Resultsmentioning

confidence: 99%

“…Differences have been described in proximaldistal airways, which our study was not able to examine. This could be explored in the future with techniques such as immunohistochemistry and in situ hybridization, although it remains difficult to find rabbit primers and antibodies [43,64].…”

Section: E Rt-qpcr Resultsmentioning

confidence: 99%

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The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

Mudri

Vanderboor

Davidson

et al. 2019

Journal of Pediatric Surgery

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Purpose: Tracheal occlusion (TO) reverses pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH), but its effect on epithelial-mesenchymal transition (EMT) in lung development remains poorly understood. The purpose of this study was to a) confirm the CDH rabbit model produced PH which was reversed by TO and b) determine the effects of CDH +/-TO on EMT pathways. Methods: CDH was created at 23 days, TO at 28 days and lung collection at 31 days gestation in fetal rabbits. Lung body weight ratio (LBWR), mean terminal bronchiole density (MTBD), and expression of mRNA and micro-RNA was determined. Results: Fifteen CDH, 15 CDH+TO, 6 sham CDH, and 15 controls were included in the study. LBWR was low in CDH while CDH+TO was similar to controls. MTBD was higher in CDH fetuses and restored to control levels in CDH+TO. miR-33 and MKI67 were increased following TO, while Lgl1 was decreased in CDH+TO. Conclusion: TO reversed PH and stimulated early Wnt signaling in CDH fetal rabbits.

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Section: E Rt-qpcr Resultsmentioning

confidence: 93%

Section: E Rt-qpcr Resultsmentioning

confidence: 99%

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The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

Mudri

Vanderboor

Davidson

et al. 2019

Journal of Pediatric Surgery

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“…144 Moreover, based on the finding that human CDH lungs have upregulated miR-200b expression, 93 Eastwood et al investigated miR-200b levels in the rabbit model. 145 In this study, the authors concluded that rabbits had variable miR-200b responses after TO, and could be used as a model to study miR-200b. 145 The rabbit model has been used also to test treatments that would address vascular remodeling.…”

Section: Interventions Tested Using the Rabbit Modelmentioning

confidence: 84%

“…145 In this study, the authors concluded that rabbits had variable miR-200b responses after TO, and could be used as a model to study miR-200b. 145 The rabbit model has been used also to test treatments that would address vascular remodeling. Rojas-Moscoso et al and Vuckovic et al reported that different soluble guanylyl cyclase activators (BAY 60-2770 and BAY 41-2272) induced relaxant responses of the pulmonary artery in vitro, as well as in vivo when administered intratracheally.…”

Section: Interventions Tested Using the Rabbit Modelmentioning

confidence: 84%

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

et al. 2019

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Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.

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Fetal lung regeneration using stem cell‐derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

et al. 2022

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The poor outcomes of babies with congenital diaphragmatic hernia (CDH) are directly related to pulmonary hypoplasia, a condition characterized by impaired lung development. Although the pathogenesis of pulmonary hypoplasia is not fully elucidated, there is now evidence that CDH patients have missing or dysregulated microRNAs (miRNAs) that regulate lung development. A prenatal therapy that supplements these missing/dysregulated miRNAs could be a strategy to rescue normal lung development. Extracellular vesicles (EVs), also known as exosomes when of small dimensions, are lipid‐bound nanoparticles that can transfer their heterogeneous cargo (proteins, lipids, small RNAs) to target cells to induce biological responses. Herein, we review all studies that show evidence for stem cell‐derived EVs as a regenerative therapy to rescue normal development in CDH fetal lungs. Particularly, we report studies showing that administration of EVs derived from amniotic fluid stem cells (AFSC‐EVs) to models of pulmonary hypoplasia promotes fetal lung growth and maturation via transfer of miRNAs that are known to regulate lung developmental processes. We also describe that stem cell‐derived EVs exert effects on vascular remodeling, thus possibly preventing postnatal pulmonary hypertension. Finally, we discuss future perspectives and challenges to translate this promising stem cell EV‐based therapy to clinical practice.

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MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia

Abstract: Hypoplastic fetal rabbit lungs display upregulation of miR-200b expression although downstream targets are not different from controls. Following TO, fetal rabbit lungs display a variable miR-200b response.

Cited by 16 publications

References 35 publications

The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

Fetal lung regeneration using stem cell‐derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

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