Characterization of CFTR protein and expression levels in a human lung cell line
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Characterization of CFTR Protein and Expression Levels in Human Lung Cell Lines
Overview of CFTR in Human Lung Cells
The cystic fibrosis transmembrane conductance regulator (CFTR) protein plays a crucial role in maintaining the proper function of epithelial cells in the lungs. Dysfunctional CFTR is the primary cause of cystic fibrosis (CF), leading to severe respiratory complications. This article synthesizes recent research on CFTR characterization and expression levels in various human lung cell lines.
CFTR Expression in NCI-H292 Cells
The NCI-H292 cell line, derived from human pulmonary mucoepidermoid carcinoma, is frequently used to study airway epithelial cell infections. Research indicates that CFTR gene expression in NCI-H292 cells is significantly lower compared to T84 cells, a colon carcinoma cell line. However, protein expression levels in NCI-H292 cells are comparable to those in T84 cells. Functional assays, such as patch clamp electrophysiology, show that CFTR in NCI-H292 cells responds to cAMP elevation similarly to T84 cells, suggesting that despite low gene expression, the CFTR protein in NCI-H292 cells is functional.
CFTR in CFBE41o- Cells
CFBE41o- cells, a bronchial epithelial cell line, are used to study CF pathogenesis. These cells can express either wild-type CFTR (WTBE) or the F508del mutant CFTR (CFBE). Studies show that CFBE cells exhibit higher chromatin accessibility and different cytokine secretion patterns compared to WTBE cells. The expression of wild-type CFTR influences the cell's epigenome and transcriptome, particularly in immunity-related pathways, highlighting the intrinsic cellular differences between these isogenic cell lines.
Inducible CFTR Expression Systems
An inducible CFTR expression system has been developed using a human cytokeratin 18 expression cassette to drive epithelium-specific expression. This system allows for controlled CFTR expression in the presence of doxycycline. Studies confirm that CFTR protein expression is dose-dependent and can be tightly regulated, providing a valuable tool for understanding CFTR's role in lung function and designing CF therapies.
CFTR in Human Lung Microvascular Endothelial Cells
CFTR expression in human lung microvascular endothelial cells (HLMVECs) is associated with the regulation of oxidative stress and inflammatory responses. Inhibition of CFTR in these cells increases oxidative stress markers and inflammatory cytokines, such as IL-8. This suggests that functional CFTR is crucial for maintaining the anti-inflammatory state of endothelial cells, and therapeutic strategies to restore CFTR function could be beneficial.
CFTR and HE4 Expression in CF Bronchial Epithelial Cells
In CF bronchial epithelial cells, CFTR dysfunction is linked to abnormal expression of human epididymis protein 4 (HE4). CFTR modulators, such as lumacaftor/ivacaftor, can partially restore CFTR function and reduce HE4 levels. This indicates that CFTR activity influences HE4 expression through the NF-κB pathway, and targeting this pathway could help manage CF-related inflammation.
Cell Type-Specific CFTR Expression
Single-cell RNA sequencing (scRNA-seq) has identified secretory cells as the primary contributors to CFTR expression in human airway epithelia. While ionocytes express the highest levels of CFTR, they are rare. Secretory cells dominate CFTR-mediated chloride secretion, suggesting that CF therapies should focus on restoring CFTR function in these cells.
Conclusion
The characterization of CFTR protein and its expression levels in various human lung cell lines provides critical insights into CF pathogenesis and potential therapeutic strategies. Despite variations in gene expression, functional CFTR protein can be present in different cell types, emphasizing the importance of targeted therapies to restore CFTR function across multiple cell types in the lung.
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Most relevant research papers on this topic
Characterization of CFTR expression in a human pulmonary mucoepidermoid carcinoma cell line, NCI‐H292 cells
Multi-omic comparisons between CFBE41o- cells stably expressing wild-type CFTR and F508del-mutant CFTR.
Regulated expression of the human CFTR gene in epithelial cells.
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Human Lung Microvascular Endothelial Cells Controls Oxidative Stress, Reactive Oxygen-Mediated Cell Signaling and Inflammatory Responses
Enhanced Expression of Human Epididymis Protein 4 (HE4) Reflecting Pro-Inflammatory Status Is Regulated by CFTR in Cystic Fibrosis Bronchial Epithelial Cells
Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia.
Characterization of wild-type and deltaF508 cystic fibrosis transmembrane regulator in human respiratory epithelia.
Submucosal glands are the predominant site of CFTR expression in the human bronchus
Gene expression profile study in CFTR mutated bronchial cell lines
miR-200b downregulates CFTR during hypoxia in human lung epithelial cells
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