A5048047602- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- Pediatric health and respiratory diseases
- Tracheal and airway disorders
- Orthopaedic implants and arthroplasty
- Pediatric Hepatobiliary Diseases and Treatments
- Total Knee Arthroplasty Outcomes
- Respiratory viral infections research
- dental development and anomalies
- Orthopedic Infections and Treatments
- Bone Tissue Engineering Materials
- Milk Quality and Mastitis in Dairy Cows
- Infant Nutrition and Health
- Hybrid Renewable Energy Systems
- Ion Transport and Channel Regulation
University of Iowa
2019-2024
Arizona Research Center
1991
Submucosal glands (SMGs) are a prominent structure that lines human cartilaginous airways. Although it has been assumed SMGs contribute to respiratory defense, hypothesis gone without direct test. Therefore, we studied pigs, which have lungs like humans, and disrupted the gene for ectodysplasin ( EDA-KO ), initiates SMG development. pigs lacked throughout Their airway surface liquid had reduced ability kill bacteria, consistent with production of antimicrobials. In wild-type secrete mucus...
Lack of CFTR (cystic fibrosis transmembrane conductance regulator) affects the transcriptome, composition, and function large small airway epithelia in people with advanced cystic (CF); however, whether lack causes cell-intrinsic abnormalities present at birth versus inflammation-dependent is unclear. We performed a single-cell RNA-sequencing census microdissected airways from newborn CF pigs, which recapitulate host defense defects pathology over time. minimally affected transcriptome...
In a newborn pig cystic fibrosis (CF) model, the ability of gland-containing airways to fight infection was affected by at least two major host-defense defects: impaired mucociliary transport and lower airway surface liquid (ASL) pH. airways, ASL pH is balanced CFTR (CF transmembrane conductance regulator) ATP12A, which, respectively, control HCO3- proton secretion. We found that, although porcine small tissue expressed amounts epithelial cultures from CF distal (diameter < 200 μm) were...
In cystic fibrosis (CF), reduced HCO
Cystic fibrosis (CF) is caused by genetic mutations of the CF transmembrane conductance regulator (CFTR), leading to disrupted transport Cl- and bicarbonate lung disease featuring bacterial colonization chronic infection in conducting airways. pigs engineered mutating CFTR develop that mimics human CF, are well-suited for investigating therapeutics. Clinical data suggest small airways play a key role early pathogenesis disease, but few preclinical studies have focused on Efficient targeted...
In contrast to pig large airways, the pH of airway surface liquid (ASL) in small airways is regulated by CFTR mediated HCO - 3 secretion and vacuolar-type H + ATPase (V-ATPase) proton secretion. We hypothesized that Cystic Fibrosis (CF), ASL acidic, V-ATPase internalized. quantified during addition an alkaline test solutions measuring changes a dependent fluorescent dye generated porcine epithelia absence presence bafilomycin A1. The pH-dependent translocation ex vivo preparations was...
Summary The small airways of humans are affected early in several lung diseases. However, because they relatively inaccessible, little is known about the epithelial cells that line these airways. We performed a single cell RNA-seq census and large wild-type pigs with disrupted cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. sequencing data showed airway epithelia had similar major types as but no ionocytes; moreover, lack expression minimal effect on transcriptome. Small...