Language
English
Publication Date
10-1-2026
Journal
American Journal of Physiology-Cell Physiology
DOI
10.1152/ajpcell.00164.2026
PMID
42750185
Abstract
Type II alveolar epithelial cell (AT2) injury has been hypothesized to contribute to pulmonary fibrosis. Cadherin-11 (CDH11) is a mediator of fibrosis and is upregulated on AT2s during lung fibrosis. Herein, the regulation of AT2 by CDH11 during pulmonary fibrosis was investigated. CDH11 levels were increased in lung samples from patients with idiopathic pulmonary fibrosis compared with those from healthy controls. CDH11 expression was inversely correlated with lung function. Cdh11-deficient mice were compared with wild-type mice in the intraperitoneal bleomycin model (IP BLM), and the role of AT2 was investigated using Cdh11 floxed-SPC-Cre mice and in vitro techniques. In the IP BLM model of pulmonary fibrosis, genetic removal of Cdh11 and CDH11 neutralization with monoclonal antibodies reduced pulmonary fibrosis and expression of epithelial injury and mesenchymal markers. Colocalization studies demonstrated that CDH11 was coexpressed with α-SMA on AT2s during fibrosis, and inhibition of CDH11 prevented CDH11 coexpression. Furthermore, CDH11 expression was associated with the expression of the AT2 transitional cell marker KRT8 in both in vivo and in vitro studies. Finally, in vitro studies demonstrated that CDH11 engagement, but not N-cadherin engagement, could drive expression of mesenchymal markers in AT2s. Finally, AT2-selective deletion of Cdh11 reduced pulmonary fibrosis in the IP BLM model, confirming that CDH11 regulates AT2 during the development of lung fibrosis. These data demonstrate that CDH11 is a key regulator of AT2 injury and mesenchymal gene expression during the development of lung fibrosis.
NEW & NOTEWORTHY This study identifies CDH11 as a key regulator of AT2 during the development of lung fibrosis and further confirms the importance of CDH11 and AT2 in the development of lung fibrosis.
Keywords
Animals, Cadherins, Alveolar Epithelial Cells, Humans, Mice, Bleomycin, Pulmonary Fibrosis, Male, Mice, Inbred C57BL, Idiopathic Pulmonary Fibrosis, Disease Models, Animal, Mice, Knockout, cadherin-11, fibrosis, type II alveolar epithelial cell
Published Open-Access
yes
Recommended Citation
Pedroza, Mesias; To, Sarah; Smith, Jennifer; et al., "Cadherin-11 Regulation of Type II Alveolar Epithelial Cells During Pulmonary Fibrosis" (2026). Faculty, Staff and Students Publications. 8743.
https://digitalcommons.library.tmc.edu/baylor_docs/8743