Polarity in respiratory development, homeostasis and disease

Tilston-Lünel, Andrew; Varelas, Xaralabos

doi:10.1016/bs.ctdb.2023.02.004

Cited by 2 publications

(3 citation statements)

References 129 publications

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“…On the one hand, cell surface and adhesion molecules guide epithelial cells entering the adjacent structures to enable lung branching morphogenesis and spatial progenitor cell distribution to provide a protective barrier. 58 On the other hand, the extracellular matrix provides a support to lung cells and is essential for biophysical and biochemical signaling between them. 59,60 In our analysis, we also found that compared to oligohydramnios+medium lung explants, oligohydramnios+AFSC-EV lung explants had 14 downregulated genes that are involved in biological processes related to extracellular space regulation, tissue development, and cell differentiation ( Fig.4B ).…”

Section: Resultsmentioning

confidence: 99%

Section: Induction Of Oligohydramnios Leads To Transcriptomic Alterat...mentioning

confidence: 99%

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Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

Doktor,

Figueira,

Fortuna

et al. 2024

Preprint

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Oligohydramnios (decreased amniotic fluid volume for gestational age) is a severe condition associated with high morbidity and mortality mainly due to fetal pulmonary hypoplasia. Currently, there are limited treatment options to promote fetal lung development. Administration of stem cells and their derivates have shown promising regenerative properties for several fetal and neonatal diseases related to arrested lung development. Herein, we first characterized pulmonary hypoplasia secondary to oligohydramnios in a surgical rat model. Experimental induction of oligohydramnios led to impaired lung growth, branching morphogenesis (fewer airspaces with decreasedFgf10,Nrp1,Ctnnb1expression), proximal/distal progenitor cell patterning (decreased Sox2 and Sox9 expression), and TGF-β signaling. We then tested antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC- EVs). In oligohydramnios lungs, AFSC-EV administration improved lung branching morphogenesis and airway progenitor cell patterning at least in part through the release of miR-93-5p. Our experiments suggest that AFSC-EV miR-93-5p blocked SMAD 7, resulting in upregulation of pSMAD2/3 and restoration of TGF-β signaling. Conversely, oligohydramnios lungs treated with antagomir 93-5p transfected AFSC- EVs had decreased branching morphogenesis and TGF-β signaling. This is the first study reporting that antenatal administration of stem cell derivatives could be a potential therapy to rescue lung development in fetuses with oligohydramnios.HighlightsPulmonary hypoplasia secondary to oligohydramnios in fetal rats is characterized by impaired TGF-β signaling.AFSC-EV administration improves fetal lung branching morphogenesis and airway progenitor cell patterning.AFSC-EV effects are mediated at least in part via modulation of TGF-β signaling by the release of miR-93-5p from AFSC-EVs.

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Section: Resultsmentioning

confidence: 99%

Section: Induction Of Oligohydramnios Leads To Transcriptomic Alterat...mentioning

confidence: 99%

Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

Doktor,

Figueira,

Fortuna

et al. 2024

Preprint

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“…The alteration of apicobasal polarity is associated with numerous pathological conditions, including cancer, autosomal dominant polycystic kidney disease, cystic fibrosis, asthma and viral infections ( Tilston-Lunel and Varelas, 2023 ; Wilson, 1997 ). Apicobasal polarity perturbations classically include the partial or complete loss of polarity, the extent of which usually correlates with the progression of the disease ( Halaoui et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Inverted apicobasal polarity in health and disease

Pasquier,

Jaulin,

Peglion

2024

Journal of Cell Science

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Apicobasal epithelial polarity controls the functional properties of most organs. Thus, there has been extensive research on the molecular intricacies governing the establishment and maintenance of cell polarity. Whereas loss of apicobasal polarity is a well-documented phenomenon associated with multiple diseases, less is known regarding another type of apicobasal polarity alteration – the inversion of polarity. In this Review, we provide a unifying definition of inverted polarity and discuss multiple scenarios in mammalian systems and human health and disease in which apical and basolateral membrane domains are interchanged. This includes mammalian embryo implantation, monogenic diseases and dissemination of cancer cell clusters. For each example, the functional consequences of polarity inversion are assessed, revealing shared outcomes, including modifications in immune surveillance, altered drug sensitivity and changes in adhesions to neighboring cells. Finally, we highlight the molecular alterations associated with inverted apicobasal polarity and provide a molecular framework to connect these changes with the core cell polarity machinery and to explain roles of polarity inversion in health and disease. Based on the current state of the field, failure to respond to extracellular matrix (ECM) cues, increased cellular contractility and membrane trafficking defects are likely to account for most cases of inverted apicobasal polarity.

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Polarity in respiratory development, homeostasis and disease

Cited by 2 publications

References 129 publications

Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

Inverted apicobasal polarity in health and disease

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