Hypercapnia limits β-catenin mediated alveolar type 2 cell progenitor function by altering Wnt production from adjacent fibroblasts
Dada, L. A.; Welch, L. C.; Magnani, N. D.; Ren, Z.; Brazee, P. L.; Celli, D.; Flozak, A. S.; Weng, A.; Maciel-Herrerias, M.; Kryvenko, V.; Vadasz, I.; Runyan, C. E.; Abdala-Valencia, H.; Shigemura, M.; Casalino-Matsuda, S. M.; Misharin, A. V.; Budinger, G. R. S.; Gottardi, C. J.; Sznajder, J. I.
Show 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 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, we show that hypercapnia limits {beta}-catenin signaling in alveolar type 2 (AT2) cells, leading to reduced proliferative capacity. Hypercapnia alters expression of major Wnts in PDGFRa+-fibroblasts from those maintaining AT2 progenitor activity and towards those that antagonize {beta}-catenin signaling and limit progenitor function. Activation of {beta}-catenin signaling in AT2 cells, rescues the inhibition AT2 proliferation induced by hypercapnia. Inhibition of AT2 proliferation in hypercapnic patients may contribute to impaired lung repair after injury, preventing sealing of the epithelial barrier, increasing lung flooding, ventilator dependency and mortality.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Acquisition of cellular properties during alveolar formation requires differential activity and distribution of mitochondria 97%
- Atf3 defines a population of pulmonary endothelial cells essential for lung regeneration 95%
- Heparan Sulfate-dependent RAGE oligomerization is indispensable for pathophysiological functions of RAGE 94%
Similar papers in this journal
- Lung injury induces alveolar type 2 cell hypertrophy and polyploidy with implications for repair and regeneration 98%
- Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis 96%
- Targeting Pulmonary Fibrosis by SLC1A5 dependent Glutamine Transport Blockade 95%
Similar papers in this journal
- Redundant and additive functions of the four Lef/Tcf transcription factors in lung epithelial progenitors 97%
- Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis 95%
- The androgen receptor in mesenchymal progenitors regulates skeletal muscle mass via Igf1 expression in male mice. 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.