miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt/ -catenin pathway

Wang, Yang; Huang, Chaoqun; Chintagari, Narendranath Reddy; Bhaskaran, Manoj; Weng, Tingting; Guo, Yujie; Xiao, Xiao; Liu, Lin

doi:10.1093/nar/gks1460

Cited by 102 publications

(77 citation statements)

References 52 publications

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“…This regulation of multiciliogenesis is in part mediated by inhibition of Notch1 and Dll1, which repress ciliated cell differentiation (Marcet et al, 2011). miR375 is another late stage miRNA that is upregulated just prior to birth in AEC2 cells and remains highly expressed postnatally (Wang et al, 2013b). If AEC2 cells are cultured on plastic plates, miR375 levels decrease, inducing trans-differentiation of AEC2 into AEC1 through upregulation of β-catenin signaling (Wang et al, 2013b).…”

Section: Epigenetic Regulators Of Lung Epithelial Cell Fate and Diffementioning

confidence: 99%

“…miR375 is another late stage miRNA that is upregulated just prior to birth in AEC2 cells and remains highly expressed postnatally (Wang et al, 2013b). If AEC2 cells are cultured on plastic plates, miR375 levels decrease, inducing trans-differentiation of AEC2 into AEC1 through upregulation of β-catenin signaling (Wang et al, 2013b). A similar trans-differentiation process occurs during development, although it is unclear whether miR375 similarly regulates this process in vivo through inhibition of β-catenin signaling.…”

Section: Epigenetic Regulators Of Lung Epithelial Cell Fate and Diffementioning

confidence: 99%

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Lung development: orchestrating the generation and regeneration of a complex organ

2014

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The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been made in defining the temporal progression of lung development, and this has led to exciting discoveries, including the derivation of lung epithelium from pluripotent stem cells and the discovery of developmental pathways that are targets for new therapeutics. These discoveries have also provided new insights into the regenerative capacity of the respiratory system. This Review highlights recent advances in our understanding of lung development and regeneration, which will hopefully lead to better insights into both congenital and acquired lung diseases. KEY WORDS: Branching morphogenesis, Epigenetics, Lung, Regeneration IntroductionThe primary function of the lungs is to exchange oxygen in the external environment with carbon dioxide in the cardiovascular system. Although this process sounds straightforward, it is fraught with multiple barriers to its success. The entire airway, like the skin, is constantly exposed to the external environment and must cope with challenges including temperature, particulate matter and allergens. Terrestrial life has adapted to these and other challenges through the evolution of a complex respiratory system consisting of a multitude of cell lineages. These cellular components are constantly communicating with each other to exchange gas efficiently while preventing blood and fluid loss and dangerous infection from pathogens.Lung development has been studied extensively in recent years, generating new insights into the origins of the different cell lineages that exist in the lung as well as the molecular pathways that regulate these lineages. This has led to novel insights into congenital lung diseases, lung abnormalities and acquired lung diseases (Box 1), including asthma and chronic obstructive pulmonary disease (COPD), and the lung's response to acute injury. In addition, these studies have revealed that some cell lineages within the mammalian respiratory system can regenerate after injury through the activation of stem/progenitor populations or through proliferation-induced cellular expansion. The molecular pathways that regulate these regenerative processes have been identified, raising the hope that these can be harnessed to promote lung regeneration in humans. Moreover, using the robust knowledge of pathways that regulate early lung development, lung epithelial cells can now be generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), providing an additional source of cells for disease modeling and potential cell-based therapies (Longmire et al., 2012;Mou et al., 2012). In this Review, we highlight recent advances in the basic understanding of lung development and regeneration with a focus on the cell biology of the developing lung epithelium, the role of endoderm progenitors, and the epigenetic regulation of lung development and regeneration. We also discuss how these adv...

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Section: Epigenetic Regulators Of Lung Epithelial Cell Fate and Diffementioning

confidence: 99%

Section: Epigenetic Regulators Of Lung Epithelial Cell Fate and Diffementioning

confidence: 99%

Lung development: orchestrating the generation and regeneration of a complex organ

2014

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“…The miR-302 family regulates epithelial progenitor proliferation and differentiation, as well as apical-basal polarity (Tian et al, 2011). Recently, miR-375 has been shown to target WNT signaling and regulate the differentiation of alveolar epithelial cells by controlling the expression of the frizzled 8 gene (Wang et al, 2013). However, miRNAs regulating WNT signaling in the lung mesenchyme have yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

miR-142-3pbalances proliferation and differentiation of mesenchymal cells during lung development

et al. 2014

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The regulation of the balance between proliferation and differentiation in the mesenchymal compartment of the lung is largely uncharacterized, unlike its epithelial counterpart. In this study, we determined that miR-142-3p contributes to the proper proliferation of mesenchymal progenitors by controlling the level of WNT signaling. miR-142-3p can physically bind to adenomatous polyposis coli mRNA, functioning to regulate its expression level. In miR-142-3p loss-of-function experiments, proliferation of parabronchial smooth muscle cell progenitors is significantly impaired, leading to premature differentiation. Activation of WNT signaling in the mesenchyme, or Apc loss of function, can both rescue miR-142-3p knockdown. These findings show that in the embryonic lung mesenchyme, the microRNA machinery modulates the level of WNT signaling, adding an extra layer of control in the feedback loop between FGFR2C and β-cateninmediated WNT signaling.

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“…Possible mechanisms which can determine cell fate during development and differentiation include methylases/demethylases (Knoblich 1997), regulators of heterochromatin remodelling (Wu and Grunstein 2000), small interfering RNAs (microRNAs and siRNAs) (Roh et al 2006;Wang et al 2009), master regulatory genes, global activator or repressors (Bird and Wolffe 1999;Surani 2001;Enver et al 2005), cell cycle regulators (Sommer and Rao 2002), and other reprogramming molecules (Bird and Wolffe 1999) (Fig. 1c).…”

Section: The Molecular Basis Of Transdifferentiationmentioning

confidence: 99%

“…Also, Wang et al showed that miR-357 is a regulator of alveolar epithelial cell transdifferentiation. They demonstrated that miR-357 controls the conversion of alveolar epithelial type II cells (AEC II) into alveolar epithelial type I cells (AEC I) through suppression of the Wnt/β-catenin signalling pathway (Wang et al 2009). More recent studies also confirmed the crucial role of miRNAs in the transdifferentiation process.…”

Section: Small Interfering Rnas: Micrornas (Mirnas) and Sirnasmentioning

confidence: 99%

Transdifferentiation: a cell and molecular reprogramming process

Sisakhtnezhad

Matin

2012

Cell Tissue Res

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Evidence has emerged recently indicating that differentiation is not entirely a one-way process, and that it is possible to convert one cell type to another, both in vitro and in vivo. This phenomenon is called transdifferentiation, and is generally defined as the stable switch of one cell type to another. Transdifferentiation plays critical roles during development and in regeneration pathways in nature. Although this phenomenon occurs rarely in nature, recent studies have been focused on transdifferentiation and the reprogramming ability of cells to produce specific cells with new phenotypes for use in cell therapy and regenerative medicine. Thus, understanding the principles and the mechanism of this process is important for producing desired cell types. Here some well-documented examples of transdifferentiation, and their significance in development and regeneration are reviewed. In addition, transdifferentiation pathways are considered and their potential molecular mechanisms, especially the role of master switch genes, are considered. Finally, the significance of transdifferentiation in regenerative medicine is discussed.

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miR-375 regulates rat alveolar epithelial cell trans-differentiation by inhibiting Wnt/ -catenin pathway

Cited by 102 publications

References 52 publications

Lung development: orchestrating the generation and regeneration of a complex organ

Lung development: orchestrating the generation and regeneration of a complex organ

miR-142-3pbalances proliferation and differentiation of mesenchymal cells during lung development

Transdifferentiation: a cell and molecular reprogramming process

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