WNT Signalling in Lung Physiology and Pathology

Hu, Yan; Ciminieri, Chiara; Hu, Qianjiang; Lehmann, Mareike; Königshoff, Mélanie; Gosens, Reinoud

doi:10.1007/164_2021_521

Cited by 15 publications

(12 citation statements)

References 196 publications

(298 reference statements)

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“…RSPO2 plays a crucial role in the activation of the WNT/B-catenin pathway, which regulates epithelial-mesenchymal crosstalk during lung development [12,68,69]. It has been described that in mouse lung development, SHH-BMP-WNT signaling is necessary for proper lung specification [70]. Based on our data, the SHH-WNT interactions also seem to be important in the patterning of the human developing lung.…”

Section: Discussionsupporting

confidence: 69%

Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis

Belgacemi

Danopoulos

Deutsch³

et al. 2022

IJMS

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The Hedgehog (HH) signaling pathway plays an essential role in mouse lung development. We hypothesize that the HH pathway is necessary for branching during human lung development and is impaired in pulmonary hypoplasia. Single-cell, bulk RNA-sequencing data, and human fetal lung tissues were analyzed to determine the spatiotemporal localization of HH pathway actors. Distal human lung segments were cultured in an air-liquid interface and treated with an SHH inhibitor (5E1) to determine the effect of HH inhibition on human lung branching, epithelial-mesenchymal markers, and associated signaling pathways in vitro. Our results showed an early and regulated expression of HH pathway components during human lung development. Inhibiting HH signaling caused a reduction in branching during development and dysregulated epithelial (SOX2, SOX9) and mesenchymal (ACTA2) progenitor markers. FGF and Wnt pathways were also disrupted upon HH inhibition. Finally, we demonstrated that HH signaling elements were downregulated in lung tissues of patients with a congenital diaphragmatic hernia (CDH). In this study, we show for the first time that HH signaling inhibition alters important genes and proteins required for proper branching of the human developing lung. Understanding the role of the HH pathway on human lung development could lead to the identification of novel therapeutic targets for childhood pulmonary diseases.

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Section: Discussionsupporting

confidence: 69%

Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis

Belgacemi

Danopoulos

Deutsch³

et al. 2022

IJMS

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“…The study design and results have been published in detail previously (Song et al, 2019). The study was approved by the Medical Ethics Committee of Zhongshan Hospital, Fudan University [ -2038[ (Hu et al, 2021], and informed consents were obtained from all patients or their legal guardians before enrollment. Eligible 710 participants enrolled at 33 centers with SCAP were randomly administered with XueBiJing (n = 334) or placebo (n = 341) for 5-7 days.…”

Section: Participants and Study Designmentioning

confidence: 99%

“…The main physiological function of the lung is gas exchange. At the same time, because it is directly exposed to the outside world, the lung is vulnerable to microbial invasion and environmental noxious particles (Hu et al, 2021). In healthy lungs, this defense function is mainly achieved through the production of epithelial barriers and surfactant proteins by alveolar cells (Ruaro et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Weaker Response to XueBiJing Treatment in Severe Community-Acquired Pneumonia Patients With Higher Body Mass Index or Hyperglycemia: A Post Hoc Analysis of a Randomized Controlled Trial

et al. 2022

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Background: Overweight and hyperglycemia might result in poor prognosis in patients with severe community-acquired pneumonia (SCAP). XueBiJing treatment could significantly improve the outcomes of patients with SCAP. We investigated the efficacy of XueBiJing injection in patients with SCAP stratified by body mass index (BMI) and fasting blood glucose (FBG).Methods: This is a post hoc analysis of XueBiJing trial, a large prospective, randomized, controlled study conducted in 33 hospitals in China. We compared data from non-overweight (BMI <24 kg/m2, n = 425) vs. overweight (BMI ≥24 kg/m2, n = 250) patients as well as non-hyperglycemia (FBG <7 mmol/L, n = 315) vs. hyperglycemia (FBG ≥7 mmol/L, n = 360) patients with XueBiJing, 100 ml, q12 h, or a visually indistinguishable placebo treatment for 5–7 days.Results: Among patients with BMI <24 kg/m2 (n = 425), 33 (15.3%), XueBiJing recipients and 52 (24.9%) placebo recipients (p = 0.0186) died within 28 days. Among patients with BMI ≥24 kg/m2 (n = 250), XueBiJing recipients still had lower mortality (XueBiJing 16.9% vs. placebo 24.2%; p = 0.2068) but without significantly statistical difference. For the FBG group, patients with FBG <7 mmol/L (n = 315), 18 (11.2%) XueBiJing recipients and 32 (20.8%) placebo recipients (p = 0.030) died within 28 days. Among patients with FBG ≥7 mmol/L (n = 360), XueBiJing recipients still had lower mortality (XueBiJing 20.2% vs. placebo 27.8%; p = 0.120) but without significantly statistical difference. The total duration of the ICU stay and the duration of mechanical ventilation were similar in both groups (p > 0.05).Conclusion: Overweight or hyperglycemia might weaken the efficacy of XueBiJing injection in the treatment of SCAP as indicated by the significant elevated risk of 28-day mortality. Additional studies are needed to validate our findings and to further understand the underlying mechanisms.

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“…The lungs are one of the few internal organs that are exposed to a wide range of environmental pollutants that include organic/inorganic/biological agents from diverse natural and anthropogenic sources and are under constant threat of developing simple to complex disorders, which can compromise the quality of life and, ultimately, even lead to death [ 4 ]. Based on the pathophysiology and mode of transmission, acute and chronic lung injuries can be broadly categorized into infectious (such as pneumonia) and non-infectious diseases (e.g., pulmonary fibrosis) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries

Bezerra

Lanzetti

Nesi³

et al. 2023

Antioxidants

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Acute and chronic lung injuries are among the leading causes of mortality worldwide. Lung injury can affect several components of the respiratory system, including the airways, parenchyma, and pulmonary vasculature. Although acute and chronic lung injuries represent an enormous economic and clinical burden, currently available therapies primarily focus on alleviating disease symptoms rather than reversing and/or preventing lung pathology. Moreover, some supportive interventions, such as oxygen and mechanical ventilation, can lead to (further) deterioration of lung function and even the development of permanent injuries. Lastly, sepsis, which can originate extrapulmonary or in the respiratory system itself, contributes to many cases of lung-associated deaths. Considering these challenges, we aim to summarize molecular and cellular mechanisms, with a particular focus on airway inflammation and oxidative stress that lead to the characteristic pathophysiology of acute and chronic lung injuries. In addition, we will highlight the limitations of current therapeutic strategies and explore new antioxidant-based drug options that could potentially be effective in managing acute and chronic lung injuries.

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WNT Signalling in Lung Physiology and Pathology

Cited by 15 publications

References 196 publications

Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis

Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis

Weaker Response to XueBiJing Treatment in Severe Community-Acquired Pneumonia Patients With Higher Body Mass Index or Hyperglycemia: A Post Hoc Analysis of a Randomized Controlled Trial

Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries

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