Wnt and FGF mediated epithelial‐mesenchymal crosstalk during lung development

Volckaert, Thomas; Langhe, Stijn P. De

doi:10.1002/dvdy.24234

Cited by 114 publications

(124 citation statements)

References 271 publications

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“…This is the first study to demonstrate a deficiency in MSC expression of FGF-10 in progressive IPF, a specific clinical endotype. This is consistent with a protective role of FGF-10 in animal models of lung injury and fibrosis24404359. Further studies are required to determine the impact of the FGF-10 deficiency on epithelial cell fate and function.…”

Section: Discussionsupporting

confidence: 76%

Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis

Chanda

Kurundkar

Rangarajan

et al. 2016

Sci Rep

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Cellular plasticity and de-differentiation are hallmarks of tissue/organ regenerative capacity in diverse species. Despite a more restricted capacity for regeneration, humans with age-related chronic diseases, such as cancer and fibrosis, show evidence of a recapitulation of developmental gene programs. We have previously identified a resident population of mesenchymal stromal cells (MSCs) in the terminal airways-alveoli by bronchoalveolar lavage (BAL) of human adult lungs. In this study, we characterized MSCs from BAL of patients with stable and progressive idiopathic pulmonary fibrosis (IPF), defined as <5% and ≥10% decline, respectively, in forced vital capacity over the preceding 6-month period. Gene expression profiles of MSCs from IPF subjects with progressive disease were enriched for genes regulating lung development. Most notably, genes regulating early tissue patterning and branching morphogenesis were differentially regulated. Network interactive modeling of a set of these genes indicated central roles for TGF-β and SHH signaling. Importantly, fibroblast growth factor-10 (FGF-10) was markedly suppressed in IPF subjects with progressive disease, and both TGF-β1 and SHH signaling were identified as critical mediators of this effect in MSCs. These findings support the concept of developmental gene re-activation in IPF, and FGF-10 deficiency as a potentially critical factor in disease progression.

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Section: Discussionsupporting

confidence: 76%

Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis

Chanda

Kurundkar

Rangarajan

et al. 2016

Sci Rep

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“…The Wnt signaling pathway is critical for lung endoderm specification and patterning of the branching lung and mesenchyme (Cohen et al, 2009; Goss et al, 2009; Harris-Johnson et al, 2009; Kadzik et al, 2014; Li et al, 2002; Miller et al, 2012; Mucenski et al, 2003; Rajagopal et al, 2008; Volckaert and De Langhe, 2015). However, the role for Wnt signaling during lung sacculation and alveologenesis is poorly understood.…”

Section: Resultsmentioning

confidence: 99%

Emergence of a Wave of Wnt Signaling that Regulates Lung Alveologenesis by Controlling Epithelial Self-Renewal and Differentiation

et al. 2016

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Alveologenesis is the culmination of lung development and involves the correct temporal and spatial signals to generate the delicate gas exchange interface required for respiration. Using a novel Wnt signaling reporter system, we demonstrate the emergence of a Wnt-responsive alveolar epithelial cell sublineage that arises during alveologenesis called the axin2+ alveolar type 2 cell or AT2Axin2. The number of AT2Axin2 cells increases substantially during late lung development, correlating with a wave of Wnt signaling during alveologenesis. Transcriptome analysis, in vivo clonal analysis, and ex vivo lung organoid assays reveal that AT2sAxin2 promote enhanced AT2 cell growth during generation of the alveolus. Activating Wnt signaling results in expansion of AT2s whereas inhibition of Wnt signaling inhibits AT2 cell development and shunts alveolar epithelial development towards the alveolar type 1 cell lineage. These findings reveal a wave of Wnt-dependent AT2 expansion required for lung alveologenesis and maturation.

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“…Since many components of the Hippo pathway (Fig. In addition, since the Hippo pathway has been shown to interact with many other pathways such as the Wnt pathway, which is critical for lung homeostasis, 93 it will be very interesting to further explore how the Hippo interacts with these known Hippo-interacting signaling pathways or identify novel signaling pathways interacting with the Hippo signaling in regulating lung development, tumorigenesis and metastasis. In addition, we and others have shown that the Hippo pathway is involved in many aspects of cancer progression and therapy such as drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Roles of the Hippo pathway in lung development and tumorigenesis

Yeung

Yang

2015

Intl Journal of Cancer

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Lung cancer is the most commonly diagnosed cancer and accounts for one fifth of all cancer deaths worldwide. Although significant progress has been made toward our understanding of the causes of lung cancer, the 5-year survival is still lower than 15%. Therefore, there is an urgent need for novel lung cancer biomarkers and drug targets. The Hippo signaling pathway is an emerging signaling pathway that regulates various biological processes. Recently, increasing evidence suggests that the Hippo pathway may play important roles in not only lung development but also lung tumorigenesis. In this review article, we will summarize the most recent advances and predict future directions on this new cancer research field.

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Wnt and FGF mediated epithelial‐mesenchymal crosstalk during lung development

Cited by 114 publications

References 271 publications

Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis

Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis

Emergence of a Wave of Wnt Signaling that Regulates Lung Alveologenesis by Controlling Epithelial Self-Renewal and Differentiation

Roles of the Hippo pathway in lung development and tumorigenesis

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