MicroRNA-200b regulates distal airway development by maintaining epithelial integrity

Khoshgoo, Naghmeh; Visser, Robin; Falk, Landon; Day, Chelsea; Ameis, Dustin; Iwasiow, Barbara; Zhu, Fuqin; Öztürk, Arzu; Basu, Sandip K.; Pind, Molly; Fresnosa, Agnes FresnosaA.; Jackson, Mike; Siragam, Vinaya Kumar; Stelmack, Gerald L.; Hicks, Geoffrey; Halayko, Andrew J.; Keijzer, Richard

doi:10.1038/s41598-017-05412-y

Cited by 39 publications

(32 citation statements)

References 42 publications

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“…The inhibition of miR-200 family in type II cells isolated from human fetal lungs decreased protein levels of SP-A, SP-B and pro-SP-C, and furthermore, reduced phospholipid-containing lamellar inclusions [32]. Similarly, in another study, knockout of miR-200b resulted in the disruption of surfactant properties, decreased lung septation, and thickened alveolar walls [33].…”

Section: The Role Of Mirnas In Some Developmental Milestones Of the Lungmentioning

confidence: 88%

miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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The development of the lung involves a diverse group of molecules that regulate cellular processes, organ formation, and maturation. The various stages of lung development are marked by accumulation of small RNAs that promote or repress underlying mechanisms, depending on the physiological environment in utero and postnatally. To some extent, the pathogenesis of various lung diseases is regulated by small RNAs. In this review, we discussed miRNAs regulation of lung development and diseases, that is, COPD, asthma, pulmonary fibrosis, and pulmonary arterial hypertension, and also highlighted possible connotations for human lung health.After fertilization in the mouse, total miRNA in the two-cell-stage embryo was demonstrated to be significantly lower than the levels in one-cell zygote [15]. Notably, total miRNA in the four-cell-stage embryo was higher than the levels in the two-cell-stage embryo [15]. In the early mouse embryo, miR-127 was upregulated at E6.5 and E7.5 [16]. Overexpression of miR-127 in mouse embryonic stem cells, which differentiated into embryoid bodies, increased the mRNA levels of Gsc, Foxa2, and Brachyury (mesendoderm markers), but elicited no change in Pax6 and Otx2 (ectoderm markers) three days after transfection. Inhibition of miR-127 showed opposite regulation of Gsc, Foxa2, and Brachyury. miR-127, moreover, was suggested to control mesendoderm differentiation [16]. miR-326 regulated sonic hedgehog signaling by targeting Smo and Gli2 [17]. The inhibition of smoothened in cultured explanted E12 mouse lung resulted in the expansion of distal epithelium, and disruption of normal branching pattern and mesenchymal integrity [17]. Another study described the functional role of miR-142-3p in the mouse embryonic lung mesenchyme. The miRNA was shown to regulate adenomatous polyposis coli to further modulate Wnt signaling [18]. Taken together, miR-142-3p regulated the proliferation and differentiation of mesenchymal progenitors in the mouse embryonic lung [18].In the developing mouse lung, the level of miR-17 was stable (E11.5-E16.5), predominantly at the pseudoglandular stage, with higher epithelial levels at E12.5 [19]. Simultaneous knockdown of miR-17 and its paralogs, miR-20a and miR-106b, for 72 h in epithelial lung explants altered branching, even in FGF10-treated condition [19]. In the human fetal lung, miR-449a was upregulated at 18-20 weeks (canalicular stage), and in the mouse embryonic lung, miR-449a level was increased from E15.5 to E18.5 [20]. The inhibition of miR-449a in E16.5 mouse lung culture (end of pseudoglandular stage) increased the mRNA levels of Mycn and Sox9, and the protein levels of Ki-67 and SOX9 particularly in the distal epithelial region [20].Knockout of miR-26a-1/miR-26a-2 in the mouse promoted the formation of dilated lumens and aerated regions at the beginning of the canalicular stage (E16.5) of lung development [21]. Results at the saccular stage (E18.5) also indicated large lamellar bodies, and increased SP-A, SP-B, and SP-C protein levels in miR-26a knockout mice....

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Section: The Role Of Mirnas In Some Developmental Milestones Of the Lungmentioning

confidence: 88%

miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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“…MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression through post-transcriptional silencing of mRNAs [19,48,49]. miRNAs work by accelerating the degradation of mRNAs or repressing translation, thereby negatively regulating the expression of target genes ( Figure 3) [50].…”

Section: F the Role Of Micrornas In Lung Development Pathwaysmentioning

confidence: 99%

“…miRNAs are therefore important in signal transduction and function as epigenetic regulators of cell signaling pathways [31,51]. miRNAs are essential for normal organogenesis during embryonic development [19,48,50]. To date, 1800 miRNAs have been identified in humans [48].…”

Section: F the Role Of Micrornas In Lung Development Pathwaysmentioning

confidence: 99%

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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“…Also, tracheal fluid from human CDH fetuses undergoing fetal endoscopic tracheal occlusion (FETO) with a treatment response (measurable lung growth and survival) had higher levels of miR‐200 family members than nonresponders . MiR‐200b knockout mice demonstrate poorer postnatal lung function, reduced surfactant protein, and overall fewer airspaces . Conversely, introduction of miR‐200b mimics in the embryonic stage of lung development to pregnant rats exposed to nitrofen improves survival and reduces the rate of diaphragmatic defects in pups .…”

Section: Introductionmentioning

confidence: 99%

“…13 knockout mice demonstrate poorer postnatal lung function, reduced surfactant protein, and overall fewer airspaces. 14 Conversely, introduction of miR-200b mimics in the embryonic stage of lung development to pregnant rats exposed to nitrofen improves survival and reduces the rate of diaphragmatic defects in pups. 15 The miR-200 family consists of 5 members: miR-200a, miR-200b, miR-429 (chromosome 1) and miR-200c and miR-141 (chromosome 12).…”

Section: Introductionmentioning

confidence: 99%