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Fibrinolytic niche is requested for alveolar type 2 cell-mediated alveologenesis and injury repair (preprint)
biorxiv; 2020.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2020.03.24.006270
ABSTRACT
ABSTRACT COVID-19, SARS, and MERS are featured by fibrinolytic dysfunction. To test the role of the fibrinolytic niche in the regeneration of alveolar epithelium, we compared the self-renewing capacity of alveolar epithelial type 2 (AT2) cells and its differentiation to AT1 cells between wild type (wt) and fibrinolytic niche deficient mice ( Plau −/− and Serpine1 Tg ). A significant reduction in both proliferation and differentiation of deficient AT2 cells was observed in vivo and in 3D organoid cultures. This decrease was mainly restored by uPA derived A6 peptide, a binding fragment to CD44 receptors. The proliferative and differential rate of CD44 + AT2 cells was greater than that of CD44 − controls. There was a reduction in transepithelial ion transport in deficient monolayers compared to wt cells. Moreover, we found a marked suppression in total AT2 cells and CD44 + subpopulation in lungs from brain dead patients with acute respiratory distress syndrome (ARDS) and a mouse model infected by influenza viruses. Thus, we demonstrate that the fibrinolytic niche can regulate AT2-mediated homeostasis and regeneration via a novel uPA-A6-CD44 + -ENaC cascade.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
Respiratory Distress Syndrome
/
COVID-19
Language:
English
Year:
2020
Document Type:
Preprint
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