ArticleJCI insight2023
Hypercapnia alters stroma-derived Wnt production to limit β-catenin signaling and proliferation in AT2 cells.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Hypercapnia Effects on Lung Function.Comprehensive Physiology · 2026Review
- Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review.International journal of molecular sciences · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Gene Expression Profiling of Pancreatic Ductal Adenocarcinoma Cells in Hypercapnia Identifies SIAH3 as a Novel Prognostic Biomarker.International journal of molecular sciences · 2025Article
- Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.JCI insight · 2025Article
- Design principles and therapeutic applications of novel synthetic WNT signaling agonists.iScience · 2024Review
- Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.JCI insight · 2024Article
- Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS).Respiratory research · 2024Review
- Alveolar epithelial regeneration in the aging lung.The Journal of clinical investigation · 2023Review
- Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
Persistent symptoms and radiographic abnormalities suggestive of failed lung repair are among the most common symptoms in patients with COVID-19 after hospital discharge. In mechanically ventilated patients with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 pneumonia, low tidal volumes to reduce ventilator-induced lung injury necessarily elevate blood CO2 levels, often leading to hypercapnia. The role of hypercapnia on lung repair after injury is not completely understood. Here - using a mouse model of hypercapnia exposure, cell lineage tracing, spatial transcriptomics, and 3D cultures - we show that hypercapnia limits β-catenin signaling in alveolar type II (AT2) cells, leading to their reduced proliferative capacity. Hypercapnia alters expression of major Wnts in PDGFRα+ fibroblasts from those maintaining AT2 progenitor activity toward those that antagonize β-catenin signaling, thereby limiting progenitor function. Constitutive activation of β-catenin signaling in AT2 cells or treatment of organoid cultures with recombinant WNT3A protein bypasses the inhibitory effects of hypercapnia. Inhibition of AT2 proliferation in patients with hypercapnia may contribute to impaired lung repair after injury, preventing sealing of the epithelial barrier and increasing lung flooding, ventilator dependency, and mortality.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.