Large-scale gene discovery in human airway epithelia reveals novel transcripts

Abstract

The airway epithelium represents an important barrier between the host and the environment. It is a first site of contact with pathogens, particulates, and other stimuli, and has evolved the means to dynamically respond to these challenges. In an effort to define the transcript profile of airway epithelia, we created and sequenced cDNA libraries from cystic fibrosis (CF) and non-CF epithelia and from human lung tissue. Sequencing of these libraries produced ∼53,000 3′-expressed sequence tags (3′-ESTs). From these, a nonredundant UniGene set of more than 19,000 sequences was generated. Despite the relatively small contribution of airway epithelia to the total mass of the lung, focused gene discovery in this tissue yielded novel results. The ESTs included several thousand transcripts (6,416) not previously identified from cDNA sequences as expressed in the lung. Among the abundant transcripts were several genes involved in host defense. Most importantly, the set also included 879 3′-ESTs that appear to be novel sequences not previously represented in the National Center for Biotechnology Information UniGene collection. This UniGene set should be useful for studies of pulmonary diseases involving the airway epithelium including cystic fibrosis, respiratory infections and asthma. It also provides a reagent for large-scale expression profiling.

Polymorphisms Associated with Expression of BPIFA1/BPIFB1 and Lung Disease Severity in Cystic Fibrosis

“…Previous studies (3,27) suggest that there is increased BPIFA1 expression in CF patients which may be a response to the chronic lung infection typically seen in these patients. These observations suggest that increased BPIFA1 expression is associated with lower lung function.…”

Targeting LUNX Inhibits Non–Small Cell Lung Cancer Growth and Metastasis

“…Toxic side effects are important factors that determine the clinical applicability of a drug. Therefore, toxicity is a question that needs to be addressed in this context, especially because LUNX has been reported to be involved in antibiosis of the upper airway, to be limited to a few nonciliated epithelial cells and to be elevated under inflammatory conditions, such as cystic fibrosis, chronic obstructive pulmonary disease, and allergic rhinitis (8,9,33,(36)(37)(38). LUNX regulates airway surface liquid volume by binding to ENaC in bronchial epithelial cultures (39).…”

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

“…CF BPIFA1 mRNA and protein expression were increased in the respiratory tract of patients with CF, and BPIFA1 was more frequently detected in microarrays of human airway epithelium from patients with CF than from non-CF patients (12,77). BPIFA1 protein staining was increased in the small airways of lung explants from patients with endstage CF undergoing lung transplantation, and this pattern of expression was different from that of normal lungs, where BPIFA1 is not detectable distal to the mainstem bronchi.…”

“…BPIFA1, or SPLUNC1 (previously known as PLUNC, LUNX, SPURT, and YY1), is one of the most widely studied PLUNC proteins. BPIFA1 was originally identified in mice in a study seeking genetic contributions to palatal malformations, and it is frequently identified in genomic and proteomic studies of healthy and diseased lung tissue and respiratory secretions (11)(12)(13)(14)(15)(16).…”