<scp>W</scp>nt5a attenuates <scp>W</scp>nt/β‐catenin signalling in human dermal papilla cells

Kwack, Mi Hee; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

doi:10.1111/exd.12101

Cited by 27 publications

(26 citation statements)

References 25 publications

(28 reference statements)

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“…Although both Wnt3a and Wnt5a belong to the Wnt family, the functions of the two proteins are counteractive. Previous studies reported that Wnt3a and Wnt5a activate different, even opposing, signaling profiles in other cells such as human dermal papilla cells (Kwack et al 2013), hematopoietic stem cells (Nemeth et al 2007), microglia (Halleskog and Schulte 2013), and several cell lines (Topol et al 2003). In agreement with these observations, we found that Wnt3a and Wnt5a counteracted the hyperoxia-induced inhibition of transdifferentiation of AECIIs to AECIs in primary AECIIs.…”

Section: Discussionsupporting

confidence: 91%

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Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of AECIIs to AECIs

Zhao

Zhang

et al. 2015

J Histochem Cytochem.

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ArticlePremature newborns often suffer from hypoxemia and acute respiratory failure. Supplemental oxygen is one of the most treatments for preterm respiratory support. It has been reported that prolonged exposure to hyperoxia results in oxidative stress-induced tissue damage in the lung, such as acute lung injury and bronchopulmonary dysplasia (BPD) (Kugelman and Durand 2011). BPD is a clinical syndrome of chronic respiratory, which can lead to hypoxemic respiratory failure and death. Advance in mechanical ventilation increases the percentage of infants surviving delivery earlier in gestation but also results in a high morbidity of BPD (Merritt et al. 2009).In animal models, retarded lung alveolization and differentiation of alveolar epithelial type II cells (AECIIs), fewer and larger alveoli, and enlarged airspace area were found in hyperoxia-exposed lungs (Dauger et al. 2003;Wang et al. 2005;Woyda et al. 2009). These damages were considered the result of the decreased proliferation of alveolar epithelium. Alveoli are lined by two morphologically and functionally different types of cells, type I alveolar epithelial cells (AECIs) and type II alveolar epithelial cells (AECIIs) (Crapo et al. 1982). AECIs cover 95% to 99% of the alveolar surface area and are responsible for gas, ions, SummaryThe aim of this study is to investigate the effect of Wnt3a in the transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I alveolar epithelial cells (AECIs) under hyperoxia condition. In the in vivo study, preterm rats were exposed in hyperoxia for 21 days. In the in vitro study, primary rat AECIIs were subjected to a hyperoxia and normoxia exposure alternatively every 24 hr for 7 days. siRNA-mediated knockout of Wnt3a and exogenous Wnt3a were used to investigate the effect of Wnt3a on transdifferentiation of AECIIs to AECIs. Wnt5a-overexpressed AECIIs were also used to investigate whether Wnt3a could counteract the effect of Wnt5a. The results showed that hyperoxia induced alveolar damage in the lung of preterm born rats, as well as an increased expression of Wnt3a and nuclear accumulation of β-catenin. In addition, Wnt3a/β-catenin signaling was activated in isolated AECIIs after hyperoxia exposure. Wnt3a knockout blocked the inhibition of the transdifferentiation induced by hyperoxia, and Wnt3a addition exacerbated this inhibition. Furthermore, Wnt3a addition blocked the transdifferentiation-promoting effect of Wnt5a in hyperoxia-exposed Wnt5a-overexpressed AECIIs. In conclusion, our results demonstrate that the activated Wnt3a/β-catenin signal may be involved in the hyperoxiainduced inhibition of AECIIs' transdifferentiation to AECIs. (J Histochem Cytochem 63:879-891, 2015)

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Section: Discussionsupporting

confidence: 91%

“…The counteractive effect of Wnt3a and Wnt5a has been reported in human dermal papilla cells (Kwack et al 2013) and lipopolysaccharide-induced mouse primary microglia (Halleskog and Schulte 2013). However, the role of Wnt3a and Wnt5a in hyperoxia-induced lung diseases has not been studied.…”

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confidence: 99%

Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of AECIIs to AECIs

Zhao

Zhang

et al. 2015

J Histochem Cytochem.

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“…It is also associated with β -catenin/TCF4 complex, and knockdown of Fermt2 leads to loss of β -catenin mediated transcription [44], ultimately affecting myogenic development. Other effectors of the β -catenin/TCF4 complex, such as Wnt, are known to be required for the hair inducing property of DP cells [45]. Background population proteins were also localized by immunofluorescence.…”

Section: Resultsmentioning

confidence: 99%

Mouse Hair Cycle Expression Dynamics Modeled as Coupled Mesenchymal and Epithelial Oscillators

et al. 2014

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The hair cycle is a dynamic process where follicles repeatedly move through phases of growth, retraction, and relative quiescence. This process is an example of temporal and spatial biological complexity. Understanding of the hair cycle and its regulation would shed light on many other complex systems relevant to biological and medical research. Currently, a systematic characterization of gene expression and summarization within the context of a mathematical model is not yet available. Given the cyclic nature of the hair cycle, we felt it was important to consider a subset of genes with periodic expression. To this end, we combined several mathematical approaches with high-throughput, whole mouse skin, mRNA expression data to characterize aspects of the dynamics and the possible cell populations corresponding to potentially periodic patterns. In particular two gene clusters, demonstrating properties of out-of-phase synchronized expression, were identified. A mean field, phase coupled oscillator model was shown to quantitatively recapitulate the synchronization observed in the data. Furthermore, we found only one configuration of positive-negative coupling to be dynamically stable, which provided insight on general features of the regulation. Subsequent bifurcation analysis was able to identify and describe alternate states based on perturbation of system parameters. A 2-population mixture model and cell type enrichment was used to associate the two gene clusters to features of background mesenchymal populations and rapidly expanding follicular epithelial cells. Distinct timing and localization of expression was also shown by RNA and protein imaging for representative genes. Taken together, the evidence suggests that synchronization between expanding epithelial and background mesenchymal cells may be maintained, in part, by inhibitory regulation, and potential mediators of this regulation were identified. Furthermore, the model suggests that impairing this negative regulation will drive a bifurcation which may represent transition into a pathological state such as hair miniaturization.

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“…The Wnt5a-mediated non-canonical Wnt pathway has been reported to antagonize the b-catenin-dependent canonical Wnt pathway by promoting the phosphorylation of b-catenin in various contexts (15,16). Most recently, Wnt5a was reported to attenuate Wnt3a-mediated elevation of b-catenin signal in hair follicle dermal papilla cells (17). Therefore, elevated levels of b-catenin phosphorylation caused by excessive epithelial Wnt5a is most likely responsible for the anagen impairment in TG mice.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Wnt5a in mouse epidermis causes no psoriasis phenotype but an impairment of hair follicle anagen development

Zhu

Huang

et al. 2014

Experimental Dermatology

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Increased Wnt5a expression has been observed in psoriatic plaques. However, whether Wnt5a overexpression directly causes psoriasis is unknown. In this study, we generated transgenic (TG) mice with epidermal Wnt5a overexpression under the control of the human K14 promoter. The skin of Wnt5a TG mice was not psoriatic, but characterized with normal proliferation and homeostasis of epidermis. Instead, these TG mice displayed impaired hair follicle transition from telogen to anagen, most likely due to impaired canonical Wnt signalling. These results suggest that increased Wnt5a expression alone is inadequate to induce psoriasis in the skin and possible involvement of Wnt5a in hair follicle cycling.

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Wnt5a attenuates Wnt/β‐catenin signalling in human dermal papilla cells

Cited by 27 publications

References 25 publications

Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of AECIIs to AECIs

Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of AECIIs to AECIs

Mouse Hair Cycle Expression Dynamics Modeled as Coupled Mesenchymal and Epithelial Oscillators

Overexpression of Wnt5a in mouse epidermis causes no psoriasis phenotype but an impairment of hair follicle anagen development

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