| Autor: |
Russell NX; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center and University of Cincinnati Honors Program., Burra K; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center. Current affiliation: Nationwide Children's Hospital Columbus OH., Shah R; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center and University of Cincinnati Honors Program Current Affiliation: Renaissance School of Medicine at Stony Brook University., Bottasso-Arias N; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center., Mohanakrishnan M; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center and University of Cincinnati Honors Program., Snowball J; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center. Current affiliation: P&G Cincinnati, OH., Ediga HH; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine., Madala SK; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine., Sinner D; Neonatology and Pulmonary Biology Perinatal Institute. Cincinnati Children's Hospital Medical Center and University of Cincinnati, College of Medicine. |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 24. Date of Electronic Publication: 2023 Aug 24. |
| DOI: |
10.1101/2023.01.10.523309 |
| Abstrakt: |
Ion channels play critical roles in the physiology and function of the nervous system and contractile tissue; however, their role in non-contractile tissue and embryonic development has yet to be understood. Tracheobronchomalacia (TBM) and complete tracheal rings (CTR) are disorders affecting the muscle and cartilage of the trachea and bronchi, whose etiology remains poorly understood. We demonstrated that trachealis muscle organization and polarity are disrupted after epithelial ablation of Wls, a cargo receptor critical for the Wnt signaling pathway, in developing trachea. The phenotype resembles the anomalous trachealis muscle observed after deletion of ion channel encoding genes in developing mouse trachea. We sought to investigate whether and how the deletion of Wls affects ion channels during tracheal development. We hypothesize that Wnt signaling influences the expression of ion channels to promote trachealis muscle cell assembly and patterning. Deleting Wls in developing trachea causes differential regulation of genes mediating actin binding, cytoskeleton organization, and potassium ion channel activity. Wnt signaling regulated expression of Kcnj13, Kcnd3, Kcnj8, and Abcc9 as demonstrated by in vitro studies and in vivo analysis in Wnt5a and β- catenin deficient tracheas. Pharmacological inhibition of potassium ion channels and Wnt signaling impaired contractility of developing trachealis smooth muscle and formation of cartilaginous mesenchymal condensation. Thus, in mice, epithelial-induced Wnt/β-catenin signaling mediates trachealis muscle and cartilage development via modulation of ion channel expression, promoting trachealis muscle architecture, contractility, and cartilaginous extracellular matrix. In turn, ion channel activity may influence tracheal morphogenesis underlying TBM and CTR. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
